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US20120302626A1 - Microrna and use thereof in identification of b cell malignancies - Google Patents

Microrna and use thereof in identification of b cell malignancies Download PDF

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US20120302626A1
US20120302626A1 US13/513,757 US201013513757A US2012302626A1 US 20120302626 A1 US20120302626 A1 US 20120302626A1 US 201013513757 A US201013513757 A US 201013513757A US 2012302626 A1 US2012302626 A1 US 2012302626A1
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Sandeep Dave
Cassandra Jacobs
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    • C12Q2600/178Oligonucleotides characterized by their use miRNA, siRNA or ncRNA

Definitions

  • sequence listing is filed with the application in electronic format only and is incorporated by reference herein.
  • sequence listing text file “WO_ASFILED_SequenceListing.txt” was created on Dec. 3, 2010, and is 262,254 bytes in size.
  • Naive B cells migrate through the circulation to lymphoid organs where they undergo the T cell-dependent germinal center reaction.
  • Adaptive immunity is acquired as specific antigen-reactive germinal center B cells differentiate into the major effector B cells of the adaptive immune system: memory cells and plasma cells. See, e.g., FIG. 1A .
  • FIG. 1A Although the role of specific transcription factors in mature B cell differentiation has been examined (see Nutt et al. Nature. 1999; 401:556-562; Chang et al. Proc Natl Acad Sci USA. 1996; 93:6947-6952; Turner et al. Cell. 1994; 77:297-306; Shaffer et al., Immunity. 2004; 21:81-93; and Schebesta et al. Curr Opin Immunol. 2002; 14:216-223), mechanisms regulating such transcription factors during mature B cell differentiation are largely unknown.
  • malignancies derived from mature B cells are known and are believed to constitute the majority of leukemias and lymphomas. Such malignancies appear to reflect defined stages of normal B cell differentiation. Diagnosis of leukemias and lymphomas can be particularly difficult because of their shared lineage. These cancers frequently display overlapping morphologies, genetic abnormalities, and expression of surface markers, which can complicate the diagnosis. However, the distinction of these tumors is clinically important because there are important differences in the treatments and expected response to treatment. Thus methods that improve the accuracy of their diagnosis should provide to improved outcomes for these patients.
  • MicroRNAs are commonly 18-22 nucleotide-long RNA molecules that regulate expression of genes. There is an increasing recognition of the role of microRNAs in oncogenesis, lineage-selection, and immune cell function, including early B cell differentiation. See Calin et al. N Engl J Med. 2005; 353:1793-1801; O'Donnell et al. Nature. 2005; 435:839-843; Chen et al. Science. 2004; 303:83-86; Lim et al. Nature. 2005; 433:769-773; Li et al. Cell. 2007; 129:147-161; Xiao et al., Nat Immunol. 2008; 9:405-414; Baltimore et al. Nat Immunol. 2008; 9:839-845; and Ventura et al. Cell. 2008; 132:875-886. However, the full extent and function of microRNA expression during mature B cell differentiation and in B cell malignancies are not known.
  • B cell malignancies Correct diagnosis of B cell malignancies is important from both a clinical standpoint and from the standpoint of setting appropriate patient expectations. A misdiagnosed B cell malignancy may lead to an inappropriate therapy, which can unnecessarily endanger the patient's life and/or be an ineffective treatment for the B cell malignancy.
  • the diagnostic distinction of Burkitt lymphoma (BL) from diffuse large B cell lymphomas (DLBCLs) can be difficult because of overlapping morphology, immunophenotype and cytogenetics. Burkitt lymphoma tumors are molecularly distinct from DLBCL, however. The difficulty and importance of obtaining the correct diagnosis in BL was highlighted by the experience of a multicenter clinical trial, CALGB trial#925119, in which nearly half of the 100 patients with an assigned diagnosis of BL were found to have another diagnosis upon further pathology review.
  • DLBCLs can also be subclassified into two different B cell malignancies, activated B-cell (ABC) DLBCL and germinal center B cell like (GCB) DLBCL.
  • ABSC activated B-cell
  • GCB germinal center B cell like
  • the prognostic information could inform the choices and expectations of patients and their physicians.
  • the important molecular differences in these subgroups form the basis of testing different targeted therapies in these patients.
  • the possibility of a differential response to therapy among ABC and GCB DLBCLs is supported by data that suggest that the benefit of receiving a proteosome inhibitor, bortozemib, is predominantly limited to those patients who have ABC DLBCL.
  • the clinical distinction of the subgroups of DLBCL using immunohistochemistry is difficult with current methods distinguishing GCB DLBCL from non-GCB DLBCL with limited success.
  • Mature B cell differentiation is important for the development of adaptive immunity. The process is also of interest because B cell malignancies are common and retain a number of features derived from their normal counterpart B cell subsets. Unlike other maturation pathways in the hematopoietic and other cell lineages, successive stages of mature B cells do not simply signify progressive differentiation away from the stem cell stage. Rather, each stage represents a specialized state with specific functions. Thus, germinal center (GC) cells interact with CD4 T cells and dendritic cells and undergo somatic hypermutation and Ig-heavy chain class-switching. On the other hand, plasma cells secrete immunoglobulin, while memory cells are primed to proliferate and differentiate into plasma cells upon repeat contact with antigen. The specialized functions demand a finely tuned program of gene regulation.
  • GC germinal center
  • MicroRNAs represent a novel class of biomarkers that provide new opportunities for clinical translation.
  • intact microRNAs can be isolated from tissues preserved using standard methods, such as formalin fixed, paraffin embedded (FFPE) tissue.
  • FFPE formalin fixed, paraffin embedded
  • microRNA-based biomarkers could be easy to translate to clinical use.
  • microRNAs can be readily assayed using real-time PCR and other methods available in conventional pathology.
  • the disclosure provides an isolated nucleic acid molecule having at least 80% sequence identity to any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof.
  • Embodiments provide for sequence identity of at least 90% or 95%.
  • an isolated nucleic acid molecule comprises any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof.
  • Embodiments provide for isolated nucleic acid molecules comprising a primary miRNA, a precursor miRNA, a mature miRNA, or a DNA molecule coding therefore.
  • Embodiments further provide for a cDNA molecule comprising sequence that corresponds to a miRNA sequence of any one of SEQ ID NOs: 763-1350 or 1565.
  • compositions, pharmaceutical compositions, vectors, host cells, and DNA libraries comprising at least one nucleic acid molecule described herein.
  • the disclosure provides a method of determining the B cell stage of a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 4.
  • the disclosure provides a method of identifying a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 4.
  • the disclosure provides a method of diagnosing a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 4.
  • the disclosure provides a method of identifying a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in any one of Tables 7 to 35.
  • the disclosure provides a method of diagnosing a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in any one of Tables 7 to 35.
  • Embodiments of these aspects provide for identification or diagnosis of a B cell malignancy selected from chronic lymphocytic leukemia, follicular lymphoma, Hodgkin's lymphoma, activated B-cell diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL, and Burkitt lymphoma.
  • a B cell malignancy selected from chronic lymphocytic leukemia, follicular lymphoma, Hodgkin's lymphoma, activated B-cell diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL, and Burkitt lymphoma.
  • the disclosure provides a method of determining whether a B cell malignancy in a sample is Burkitt lymphoma, activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 10, column “BL miRNA list”; Table 14, column “BL High”; Table 11; Table 14, column “ABC High”; Table 10, column “GCB miRNA list”; Table 14, column “GCB High”; Table 32, or Table 35.
  • the disclosure provides a method of determining whether a B cell malignancy in a sample is Burkitt lymphoma, activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in at least one column labeled “GCBvsBL” or “GCBvsABC” in Table 7 or “ABCvsBL” in Table 8.
  • the disclosure provides a method of determining whether a B cell malignancy in a sample is activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 35.
  • DLBCL diffuse large B cell lymphoma
  • the disclosure provides a microarray comprising miRNA-specific probe oligonucleotides wherein at least one miRNA-specific probe oligonucleotide is specific for a sequence of SEQ ID NOs: 763-1350 or 1565, or any combination thereof.
  • the disclosure provides a kit comprising at least one primer sequence that can detect any one of SEQ ID NOs: 763-1350 or 1565, or a combination thereof.
  • the disclosure provides a kit comprising at least one isolated nucleic acid molecule having a sequence of any one of SEQ ID NOs: 1351-1564.
  • the disclosure provides a method of identifying a B cell malignancy comprising determining the level of expression of at least one microRNA selected from the microRNAs listed in Table 4. In certain embodiments, a method comprises determining the level of expression of at least one microRNA selected from the microRNAs listed in Tables 7-35.
  • FIG. 1 shows that mature B cell subsets demonstrate distinct microRNA profiles.
  • FIG. 1A is a diagram showing the overall schema of mature B cell differentiation.
  • FIG. 1B shows selection of B cell subsets using flow cytometry.
  • FIG. 1C shows the distinction between naive and memory B cells based on IgD and CD27 expression using flow cytometry.
  • FIG. 1D shows relative expression of microRNA in the naive to germinal center B cell transition.
  • FIG. 1E shows relative expression of mRNA in the naive to germinal center B cell transition.
  • FIG. 1F shows relative expression of microRNA in the germinal center B cell to plasma cell transition.
  • FIG. 1G shows relative expression of mRNA in the germinal center B cell to plasma cell transition.
  • FIG. 1A is a diagram showing the overall schema of mature B cell differentiation.
  • FIG. 1B shows selection of B cell subsets using flow cytometry.
  • FIG. 1C shows the distinction between naive and memory B cells based on
  • FIG. 1H shows relative expression of microRNA in the germinal center B cell to memory B cell transition.
  • FIG. 1I shows relative expression of mRNA in the germinal center B cell to memory B cell transition.
  • miRNAs that were, on average, at least 2-fold differentially expressed at a false discovery rate of less than 5% are shown according to the color scale.
  • mRNAs that were, on average, at least 2-fold differentially expressed at a false discovery rate of less than 1% are shown according to the color scale.
  • FIG. 1J shows that expression of certain microRNA processing genes, DGCR8, DICER1, EIF2C2, DROSHA, and XP05 is unchanged among the B cell subsets (P>0.1 in all cases).
  • FIG. 2 shows experimental validation of the interaction of miR-223, which is expressed highly in naive and memory B cells compared to germinal center B cells, and targets the transcription factor LM02.
  • FIG. 2A shows base-pairing of the 3′UTR of the LM02 gene with nucleotides 1-8 of miR-223. This 8-mer is highly conserved across a number of species and serves as a potential binding site for miR-223.
  • FIG. 2B shows the effects of over-expression of miR-223 in germinal center lymphoma-derived BJAB cells in 3 separate experiments.
  • FIG. 2C shows the relative LM02 protein expression from a representative experiment (from 3 replicates) transfecting a scrambled control versus a precursor for miR-223 in BJAB cells.
  • FIG. 2A shows base-pairing of the 3′UTR of the LM02 gene with nucleotides 1-8 of miR-223. This 8-mer is highly conserved across a number of species and serves as a potential binding site for
  • FIG. 2D shows average expression of LM02 relative to Actin over three Western blots of BJAB cells transfected with a scrambled control versus a precursor for miR-223.
  • FIG. 2E shows luciferase activity in BJAB cells transfected with a vector comprising either a luciferase gene coupled to the 3 ′UTR of the LM02 gene or a luciferase gene coupled to the 3 ′UTR of the LM02 gene with the miR-223 binding site mutated, and cotransfected with miR-223.
  • FIG. 3 shows experimental validation of the interaction of miR-9 and miR-30, which are expressed highly in germinal center B cells compared to plasma cells and target the transcription factor PRDM1.
  • FIG. 3A shows base-pairing of the 3′UTR of the PRDM1 gene with the 5′ seed region of miR-9 and the miR-30 family.
  • FIG. 3B shows the effects of over-expressing miR-9 and 2 members of the miR-30 family, miR-30b and miR-30d, in plasma cell myeloma-derived U266 cells in 3 separate experiments.
  • FIG. 3C shows the relative PRDM1 protein expression from a representative experiment (from 3 replicates) transfecting a scrambled control versus a precursor for miR-9, miR-30b, or miR-30d in U266 cells.
  • FIG. 3E shows repression of luciferase activity from the PRDM1 3′UTR construct by overexpression of miR-9, miR-30b, and miR-30d wild-type and mutant sequences.
  • FIG. 4 shows that expression of microRNAs in normal B cells is conserved in certain B cell malignancies.
  • FIG. 4A shows lineage prediction of both IgV mutated and unmutated chronic lymphocytic leukemia, germinal center B cell derived DLBCL, and Burkitt lymphoma based on differential expression of microRNAs in normal na ⁇ ve B cells and germinal center B cells (microRNAs depicted in FIG. 1D ).
  • FIG. 4B shows miRNAs that were found to be differentially expressed (P ⁇ 0.05) in malignant cells and normal cells as discussed in Example 5.
  • FIG. 4A shows lineage prediction of both IgV mutated and unmutated chronic lymphocytic leukemia, germinal center B cell derived DLBCL, and Burkitt lymphoma based on differential expression of microRNAs in normal na ⁇ ve B cells and germinal center B cells (microRNAs depicted in FIG. 1D ).
  • FIG. 4B shows miRNAs that were found to be differential
  • FIG. 4D shows differentially expressed miRNAs that distinguish Burkitt lymphoma, activated B cell-like (ABC) diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL (GCB DLBCL), and chronic lymphocytic leukemia. Predictor miRNAs from each pair-wise comparison that distinguish each entity are shown in the boxes.
  • FIG. 5 shows the distribution of miRNAs present in B-cell subsets.
  • FIG. 6 shows that certain microRNA targets are expressed at lower levels.
  • FIG. 6A shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in germinal center B cells compared to naive cells.
  • FIG. 6B shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in germinal center B cells compared to plasma cells.
  • FIG. 6C shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in the germinal center B cells compared to memory B cells.
  • FIG. 7 shows that differentially expressed transcription factors are frequently microRNA targets.
  • the left panel indicates the proportion of transcription factors that are differentially expressed in the naive to germinal center B-cell transition that are also predicted targets of differentially expressed miRNAs.
  • the right panel indicates the proportion of transcription factors that are not differentially expressed and also are predicted targets of differentially expressed miRNA in that stage-transition.
  • the p-value indicates the results of a chi-squared test for the enrichment of predicted miRNA targets among the differentially expressed transcription factors.
  • FIG. 7B shows a similar analysis of the germinal center to plasma cell transition.
  • FIG. 7C shows a similar analysis of the germinal center to memory cell transition.
  • FIG. 8 shows that Mybl transcript levels decrease with miR-223 overexpression.
  • FIG. 8A shows base-pairing of the 3′UTR of the MYBL1 gene with nucleotides 2-8 of miR-223. This 7-mer is highly conserved across a number of species and serves as a potential binding site for miR-223.
  • FIG. 8B shows the effects of over-expression of miR-223 in germinal center lymphoma-derived BJAB cells in 3 separate experiments.
  • FIG. 9 shows the specificity of real-time PCR probes for members of the miR-30 family.
  • FIG. 10 shows the results of leave one out cross validation applied to the predictors for Burkitt lymphoma, chronic lymphocytic leukemia, activated B-cell diffuse large B-cell lymphoma, and germinal center B-cell DLBCL.
  • FIG. 11 shows differentially expressed miRNAs that distinguish activated B cell-like diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL (GCB DLBCL), Burkitt lymphoma, chronic lymphocytic leukemia, follicular lymphoma, and Hodgkin's lymphoma. Predictor miRNAs from each pair-wise comparison that distinguish each entity are shown in the boxes.
  • DLBCL diffuse large B cell lymphoma
  • GCB DLBCL germinal center-like DLBCL
  • Burkitt lymphoma Burkitt lymphoma
  • chronic lymphocytic leukemia follicular lymphoma
  • Hodgkin's lymphoma Hodgkin's lymphoma
  • the disclosure relates to nucleic acid sequences, such as microRNAs (miRNA), as well as to the identification and analysis of microRNA expression levels and/or patterns in B cells.
  • miRNA microRNAs
  • the inventors have identified regulatory roles for microRNAs at each stage in mature B cell differentiation. This provides methods identifying microRNA-mediated regulation of oncogenes and key transcription factors in B cell differentiation. This work establishes the landscape of normal microRNA expression in mature B cells and its role in regulating normal B cell differentiation. Further, our work demonstrates that in contrast to the described down-regulation in other malignancies, stage-specific microRNAs are retained in B cell malignancies. The lineage of common B cell malignancies can be predicted based upon miRNA profiles of normal B cells, pointing to a role for microRNAs in the maintenance of mature B cell phenotypes in normal and malignant B cells.
  • the disclosure relates to an isolated nucleic acid molecule comprising: (a) a nucleotide sequence as shown in Table 32; (b) a nucleotide sequence which is the complement of (a), (c) a nucleotide sequence comprising a sequence identity of at least 80%, (e.g., 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or at least 99%), to a sequence of (a) or (b) and/or (d) a nucleotide sequence which hybridizes under stringent conditions to a sequence of (a), (b) and/or (c).
  • sequence (c) to a sequence of (a) or (b) is at least 90%. In other embodiments, the identity of sequence (c) to a sequence of (a) or (b) at least 95%.
  • the percent identity can be calculated by any routine method used by one of skill in the art such as, for example, the methods described herein.
  • the isolated nucleic acid molecule relates to a miRNA molecule and analogs thereof, a miRNA precursor molecule, or a primary miRNA molecule, as well as to DNA molecules encoding miRNA, miRNA precursor, or primary miRNA molecules. Accordingly, in such embodiments, the isolated nucleic acid molecule can function as a miRNA molecule under suitable conditions. Suitable conditions include, but are not limited to, various buffer systems that approximate physiologically relevant ionic concentrations and pHs, as well as physiological conditions.
  • the nucleic acid molecule comprises a sequence that hybridizes to a nucleotide sequence as shown in Table 32, a complementary sequence thereof or a nucleic acid molecule having at least 80% sequence identity under stringent hybridization conditions.
  • the basic parameters affecting the choice of hybridization conditions and guidance for devising suitable conditions are set forth by Sambrook, et al. (See, 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; and Current Protocols in Molecular Biology, 1995, Ausubel et al., eds., John Wiley & Sons, Inc.), and can be readily determined by those of ordinary skill in the art based on, for example, the length and/or base composition of the DNA.
  • stringent salt concentration will ordinarily be less than about 750 mM NaCl and 75 mM trisodium citrate, or less than about 500 mM NaCl and 50 mM trisodium citrate, or even less than about 250 mM NaCl and 25 mM trisodium citrate.
  • High stringency hybridization conditions can be obtained by adding an amount of organic solvent (e.g., at least about 35% to about 50% formamide).
  • Stringent temperature conditions will ordinarily include temperatures of at least about 30° C., (e.g., at least about 37° C., 42° C., 45° C., 50° C., or 55° C.).
  • Varying additional parameters such as hybridization time, the concentration of detergent (e.g., 0.1-1.0% sodium dodecyl sulfate (SDS)), and the inclusion or exclusion of carrier DNA (e.g., about 100-200 ⁇ g/ml denatured salmon sperm DNA (ssDNA)), are well known to those skilled in the art.
  • concentration of detergent e.g., 0.1-1.0% sodium dodecyl sulfate (SDS)
  • carrier DNA e.g., about 100-200 ⁇ g/ml denatured salmon sperm DNA (ssDNA)
  • Stringent hybridization conditions include non-limiting examples such as, washing for 1 hr in 300 mM NaCl, 30 mM trisodium citrate and 0.1% SDS at 45-50° C.; washing for 1 h in 300 mM NaCl, 30 mM trisodium citrate and 0.1% SDS at 45-50° C.; in 500 mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 ⁇ g/ml denatured salmon sperm DNA (ssDNA) at 37° C.; or in 250 mM NaCl, 25 mM trisodium citrate, 1% SDS, 50% formamide, and 200 ⁇ g/ml ssDNA at 42° C. Useful variations on these conditions will be readily apparent to those skilled in the art.
  • the isolated nucleic acid molecules provided herein suitably have a length of from about 18 to about 100 nucleotides.
  • the lengths of the miRNAs are suitably in an expected range for the particular type of miRNA molecule.
  • mature miRNAs are typically from about 15 to about 28 nucleotides in length, and suitably have a length of about 19 to about 24 nucleotides (e.g., 19, 20, 21, 22, 23, or 24 nucleotides).
  • Precursor miRNAs typically comprise the mature miRNA sequence and contain a stem-loop structure, suitably of length of about 50 to about 90 nucleotides (e.g., 50, 55, 60, 65, 70, 75, 80, 85, or 90 nucleotides).
  • Primary miRNAs e.g., a primary transcript comprising a precursor miRNA
  • the nucleic acid molecules can be provided in either a single-stranded or double-stranded form.
  • a miRNA as such is identified as a single-stranded molecule, while the precursor miRNA is typically at least partially self-complementary and capable of forming double-stranded portions, e.g. stem- and loop-structures.
  • DNA molecules encoding the miRNA and miRNA precursor molecules are typically double-stranded.
  • the individual nucleic acids that comprise the isolated nucleic acid molecules can be selected from RNA, DNA, or nucleic acid analog molecules, such as chemically modified sugar (e.g., 2′-modified (2′-F, 2′-OMe, etc.) or backbone (e.g., phosphorothioates), or cap (e.g., 5′- and/or 3′-abasic groups) moieties of ribonucleotides or deoxyribonucleotides.
  • Other nucleic acid analogs such as peptide nucleic acids (PNA) or locked nucleic acids (LNA), are also suitable in various embodiments described herein.
  • the nucleic acid molecules can comprise any combination of nucleic acid analog(s).
  • RNA sequences e.g., miRNAs
  • the disclosure of those sequences should be understood to encompass the corresponding DNA (e.g., cDNA) sequences, wherein the uracil (U) nucleotides of the disclosed RNAs are substituted by thymidine (T) nucleotides in the corresponding DNA.
  • U uracil
  • T thymidine
  • One of skill in the art is able to generate such DNA sequences (e.g., cDNA) through routine microbiological techniques known in the art such as, for example, reverse transcription using methods that incorporate the reverse transcriptase enzyme.
  • the disclosure provides a recombinant expression vector comprising a recombinant nucleic acid sequence operatively linked to an expression control sequence, wherein expression of the recombinant nucleic acid sequence provides a miRNA sequence, a precursor miRNA sequence, or a primary miRNA sequence as described herein.
  • the resulting sequence e.g., primary or precursor miRNAs
  • the recombinant expression vector comprises at least one sequence in Table 32. Any suitable expression vector can be used such as, for example, a DNA vector (e.g., viral vector, plasmid, etc.).
  • the expression vector is selected for expression in a eukaryotic cell such as, for example, a mammalian cell.
  • a eukaryotic cell such as, for example, a mammalian cell.
  • a mammalian cell such as, for example, a mammalian cell.
  • One of skill in the art will be able to select an appropriate vector based on the particular application and/or expression system to be employed.
  • nucleic acid constructs in the form of plasmids, vectors, transcription or expression cassettes which comprise at least one nucleotide sequence encoding a miRNA described herein, or fragments thereof, and a suitable promoter region.
  • Suitable vectors can be chosen or constructed, which contain appropriate regulatory sequences, such as promoter sequences, terminator sequences, polyadenylation sequences, enhancer sequences, marker genes and other sequences as desired.
  • Vectors can be plasmids, phage (e.g. phage, or phagemid) or viral (e.g. lentivirus, adenovirus, AAV) or any other appropriate vector.
  • phage e.g. phage, or phagemid
  • viral e.g. lentivirus, adenovirus, AAV
  • identity refers to a relationship between the sequences of two or more two or more nucleic acid molecules, as determined by comparing the sequences.
  • identity also means the degree of sequence relatedness between amino acid or nucleic acid molecule sequences, as the case may be, as determined by the match between strings of nucleotide or amino acid sequences. “Identity” measures the percent of identical matches between two or more sequences with gap alignments addressed by a particular mathematical model or computer programs (i.e., “algorithms”).
  • Non-limiting methods for determining identity are designed to give the largest match between the sequences tested. Methods to determine identity are codified in publicly available computer programs. Preferred computer program methods to determine identity between two sequences include, but are not limited to, the GCG program package, including GAP (Devereux, et al., Nucleic Acids Research 12:387 [1984]; Genetics Computer Group, University of Wisconsin, Madison, Wis.), BLASTN, and FASTA (Atschul et al., J. Molec. Biol. 215:403-410 [1990]).
  • the BLAST X program is publicly available from the National Center for Biotechnology Information (NCBI) and other sources (BLAST Manual, Altschul] et al., NCB NLM NIH Bethesda, Md. 20894; Altschul et al., J. Mol. Biol. 215:403-410 [1990]).
  • NCBI National Center for Biotechnology Information
  • the well known Smith Waterman algorithm may also be used to determine identity.
  • Exemplary parameters for nucleic acid molecule sequence comparison include the following:
  • the GAP program is also useful with the above parameters.
  • the aforementioned parameters are the default parameters for nucleic acid molecule comparisons.
  • gap opening penalties can be used by those of skill in the art, including those set forth in the Program Manual, Wisconsin Package, Version 9, September 1997.
  • the particular choices to be made will depend on the specific comparison to be made, such as DNA to DNA or RNA to DNA; and additionally, whether the comparison is between given pairs of sequences (in which case GAP or BestFit are generally preferred) or between one sequence and a large database of sequences (in which case FASTA or BLASTA are preferred).
  • the disclosure provides a vector comprising the isolated polynucleotide as described herein such as, for example one or more of SEQ ID NOs 773-1046 or 1450-1542.
  • the vector can be any type of vector that finds use as a vehicle to transfer foreign genetic material into a cell.
  • Non-limiting examples of vectors include plasmids, viral vectors (e.g., derived from lentivirus, adenovirus, adeno-associated virus (AAV), retrovirus, etc.), bacteriophage, cosmids, and artificial chromosomes.
  • the vector can be an expression (or expression constructs) for driving expression of the polynucleotide in a target cell. Vectors and methods for inserting them into a target cell are known in the art [See, e.g., Sambrook et al., 1989].
  • the disclosure provides recombinant cells that comprise the vectors and/or polynucleotides described herein.
  • the cells can be any cell suitable as a host for recombinant nucleic acid molecules, and selected based on well known techniques. Techniques for generating and maintaining recombinant cells are known in the art, such as those described in Sambrook et al., 1989.
  • B cell malignancy refers to a malignancy derived from any stage of B cell, including, but not limited to, na ⁇ ve cells, germinal center cells, memory B cells, and plasma cells.
  • B cell malignancies include, but are not limited to, mantle cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, germinal center B-cell like diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, and activated B-cell like DLBCL.
  • DLBCL diffuse large B cell lymphoma
  • the disclosure provides a method of distinguishing B cell malignancies on the basis of the B-cell origin.
  • methods of diagnosing B cell malignancies on the basis of the B-cell origin are provided.
  • a B cell malignancy is determined to be derived from a particular B-cell stage.
  • the B-cell origin of a B cell malignancy may be determined, in certain embodiments, by detecting one or more microRNAs that can be used to distinguish B-cell stages.
  • Certain exemplary B-cell stages include, but are not limited to, na ⁇ ve cells, germinal center cells, memory B cells, and plasma cells.
  • Certain exemplary microRNAs that can be used to distinguish B-cell stages are shown in Table 4.
  • the method comprises detecting at least one, at least two, at least five, at least 10, at least 20, at least 30, at least 50, at least 75, or at least 100 microRNAs.
  • a panel of microRNAs is selected that will allow determination of the B cell stage from which a B cell malignancy is derived.
  • two or more microRNAs from Table 4 are selected such that detection of the levels of those microRNAs in a B cell malignancy will indicate whether the B cell malignancy is derived from na ⁇ ve, germinal center, plasma, or memory B cells.
  • the panel of microRNAs comprises at least one, at least two, at least five, at least 10, at least 20, at least 30, at least 50, at least 75, or at least 100 microRNAs from Table 4.
  • One skilled in the art can select a suitable panel of microRNAs, including one or more microRNAs from Table 4, according to the intended use of the panel.
  • the methods herein can include detecting one or a plurality of miRNAs.
  • at least is used in association with a number (e.g., “at least 20”) that term will be understood to include 20 as well as optionally any integer after 20 and up to and including the total number of microRNAs disclosed herein.
  • a B cell malignancy derived from na ⁇ ve cells is mantle cell lymphoma.
  • a B cell malignancy derived from germinal center cells includes, but is not limited to, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, or germinal center B-cell like diffuse large B cell lymphoma (DLBCL).
  • a B cell malignancy derived from memory B cells includes, but is not limited to, chronic lymphocytic leukemia or small lymphocytic lymphoma.
  • a B cell malignancy derived from plasma cells includes, but is not limited to, multiple myeloma or activated B-cell DLBCL.
  • Burkitt lymphoma and DLBCLs are often confused.
  • mantle cell lymphoma and small lymphocytic lymphoma can also be confused.
  • Burkitt lymphoma and germinal center DLBCL are both derived from germinal center cells, while activated B-cell DLBCL is derived from plasma cells.
  • microRNA analysis can be used to narrow down the B cell malignancy to either a germinal center cell-derived B cell malignancy or a plasma cell-derived B cell malignancy. If the B cell malignancy is plasma-cell derived, then it may be activated B-cell DLBCL.
  • microRNAs that distinguish certain B cell stages can be used to further narrow down the identity of the B cell malignancy.
  • microRNAs that distinguish certain B cell stages can be used to identify the B cell malignancy.
  • One or more such microRNAs can be selected, in certain embodiments, from the microRNAs in Table 4.
  • One skilled in the art can select a suitable set of microRNAs, including at least one microRNA from Table 4, for distinguishing particular B cell stages.
  • the disclosure provides a method of identifying a B cell malignancy comprising detecting one or a plurality of microRNAs.
  • the method can provide a diagnosis of a B cell malignancy.
  • one or more microRNAs that are characteristic of a particular B cell malignancy are used to identify the B cell malignancy.
  • the identity of the B cell malignancy is first narrowed down to a list of two or more particular B cell malignancies using, for example, tumor morphology and/or immunohistochemistry and/or microRNA detection, e.g., to determine the B cell stage from which the tumor is derived.
  • Certain exemplary microRNAs that can be used to identify B cell malignancies are shown in the Tables (e.g., Tables 7-35).
  • methods of identifying B cell malignancies comprise detecting one or more microRNAs from one or more of Tables 7 to 15, and Appendix B, Tables 16 to 30. That is, in certain embodiments, a panel of microRNAs is selected that will identify a B cell malignancy as being one of a particular selection of B cell malignancies. As a non-limiting example, a panel of microRNAs can be designed to identify a B cell malignancy as one of Burkitt lymphoma, ABC DLBCL, or GCB DLBCL.
  • the panel of microRNAs comprises at least one microRNA from Table 10, column “BL miRNA list” and/or Table 14, column “BL High”; at least one microRNA from Table 11 and/or Table 14, column “ABC High”; and at least one microRNA from Table 10, column “GCB miRNA list” and/or Table 14, column “GCB High”.
  • microRNAs can be used to confirm that identification.
  • a B cell malignancy is believed to be a Burkitt lymphoma
  • that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 10, column “BL miRNA list” and/or Table 14, column “BL High”.
  • a B cell malignancy is believed to be ABC DLBCL
  • that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 11 and/or Table 14, column “ABC High”.
  • a B cell malignancy is believed to be GCB DLBCL, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 10, column “GCB miRNA list” and/or Table 14, column “GCB High”. If a B cell malignancy is believed to be chronic lymphocytic leukemia, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 12 and/or Table 15, column “CLL High”. If a B cell malignancy is believed to be Hodgkin's lymphoma, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 13 and/or Table 15, column “HL High”. If a B cell malignancy is believed to be follicular lymphoma, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 10, column “FL miRNA list” and/or Table 15, column “FL High”.
  • the identity of a B cell malignancy when the identity of a B cell malignancy has been narrowed down to two B cell malignancies selected from Burkitt lymphoma, GCB DLBCL, ABC DLBCL, chronic lymphocytic leukemia, follicular lymphoma, and Hodgkin's lymphoma, the identity of the B cell malignancy can be determined by detecting one or more microRNAs from Tables 16 to 30.
  • the miRNAs described herein as differentially expressed in a B cell malignancy have been identified with high confidence, and thus, identification of one miRNA is adequate to perform the methods of identification and diagnosis disclosed herein. Accordingly, in various embodiments, the methods can comprise detecting at least one, at least two, at least five, at least 10, at least 20, at least 30, or at least 50 microRNAs in order to narrow down the identity of, or identify, a B cell malignancy.
  • the treatment regimens and prognoses for the various B cell malignancies can differ significantly.
  • determining the correct identity and/or origin of a B cell malignancy can be important for selecting an effective therapy and/or setting appropriate patient expectations.
  • B cell malignancy samples may be obtained and prepared using methods known in the art.
  • One skilled in the art can select an appropriate method of obtaining a B cell malignancy sample according to various parameters, such as the age, size, medical history, and/or identity of the patient.
  • One skilled in the art can select an appropriate method of preparing a B cell malignancy sample for analysis according to the B cell malignancy sample source, size, quality, and/or intended use.
  • a B cell malignancy sample is prepared in a manner that preserves microRNAs in the sample as much as practicable under the circumstances.
  • MicroRNAs can be detected using any method known in the art. Exemplary methods of detecting microRNAs include, but are not limited to, hybridization-based methods and amplification-based methods. Certain exemplary detection methods include, but are not limited to, arrays (including microarrays and bead-based arrays), in situ hybridization, Northern blotting, TaqMan probes, RT-PCR, real-time PCR, and direct sequencing. One skilled in the art can select a suitable detection method according to the sample source, size, quality, and/or particular application.
  • real-time PCR is employed to determine the expression level of a microRNA.
  • a miRNA is considered present in a subpopulation if the cycling time (CT) is less than 36 in all three biological replicates, and a CT greater than 36 is undetected.
  • the expression level of a microRNA in a sample is determined relative to a control sample.
  • a control sample may be selected, in various embodiments, because it is expected to have either high or low expression of the microRNA.
  • the expression level of a microRNA may be normalized to the expression level of a polynucleotide that is expected to be expressed at similar levels in several different cell types and/or at constant levels in the cell type being analyzed.
  • an identified miRNA from Tables 7-35 is used to distinguish one of the six exemplified B cell malignancies from the other malignancies.
  • a “high” and a “low” in Tables 10 to 13 refer to at least a 2-fold difference in the expression of the identified miRNA when one lymphoma is compared to other lymphomas and benign lymph nodes.
  • mRNA levels can be profiled by using a microarray.
  • array elements with median signal intensities of less than 7 log 2 units across samples are removed from analysis.
  • a gene is considered for further analysis if it is on-average 2-fold or higher differentially expressed in a binary comparison of B cell subsets and expressed in at least one of the two B cell subsets being compared.
  • the level of at least one miRNA is measured by reverse transcribing RNA from a test sample obtained from a subject to provide a set of target oligodeoxynucleotides, hybridizing the target oligodeoxynucleotides to one or more miRNA-specific probe oligonucleotides (e.g., a microarray that comprises miRNA-specific probe oligonucleotides) to provide a hybridization profile for the test sample, and comparing the test sample hybridization profile to a hybridization profile generated from a control sample.
  • An alteration in the signal of at least one miRNA in the test sample relative to the control sample is indicative of the subject either having, or being at risk for developing, a B-cell malignancy.
  • the signal of at least one miRNA is upregulated, relative to the signal generated from the control sample. In another embodiment, the signal of at least one miRNA is down-regulated, relative to the signal generated from the control sample.
  • the microarray comprises miRNA-specific probe oligonucleotides for a substantial portion of all known human miRNAs. In a further embodiment, the microarray comprises miRNA-specific probe oligonucleotides for one or more miRNAs selected from the group consisting of SEQ ID NOs: 763-1350, or 1565 and any combination thereof.
  • the microarray can be prepared from gene-specific oligonucleotide probes generated from known miRNA sequences.
  • the array may contain two different oligonucleotide probes for each miRNA, one containing the active, mature sequence and the other being specific for the precursor of the miRNA.
  • the array may also contain controls, such as one or more mouse sequences differing from human orthologs by only a few bases, which can serve as controls for hybridization stringency conditions.
  • tRNAs and other RNAs e.g., rRNAs, mRNAs
  • sequences are selected based upon the absence of any homology with any known miRNAs.
  • the microarray may be fabricated using techniques known in the art. For example, probe oligonucleotides of an appropriate length, e.g., 40 nucleotides, are 5′-amine modified at position C6 and printed using commercially available microarray systems. Labeled cDNA corresponding to the target RNA sequence(s) is prepared by reverse transcribing the target RNA with labeled primer. Following first strand synthesis, the RNA/DNA hybrids are denatured to degrade the RNA templates. The labeled target cDNAs thus prepared are then hybridized to the microarray chip under typical hybridizing conditions. At positions on the array where the immobilized probe DNA recognizes a complementary target cDNA in the sample, hybridization occurs.
  • probe oligonucleotides of an appropriate length, e.g. 40 nucleotides, are 5′-amine modified at position C6 and printed using commercially available microarray systems.
  • Labeled cDNA corresponding to the target RNA sequence(s) is prepared by
  • the labeled target cDNA marks the exact position on the array where binding occurs, allowing automatic detection and quantification.
  • the output consists of a list of hybridization events, indicating the relative abundance of specific cDNA sequences, and therefore the relative abundance of the corresponding complementary miRNAs, in the patient sample.
  • kits can be used in methods of identifying a miRNA or mRNA described herein; an expression level or expression pattern of one or more miRNA(s) or mRNA(s) described herein; and/or identifying a B-cell malignancy.
  • the kit can provide a diagnosis of a B-cell type and or a B-cell malignancy.
  • the kit can differentiate one B-cell malignancy from other B-cell malignancies (e.g., ABC-DLBCL from GBC-DLBCL), and can provide information useful to a medical professional regarding a preferred course of therapeutic treatment.
  • a kit can comprise an isolated nucleic acid molecule or a plurality of isolated nucleic acid molecules as described herein (e.g., a sequence complementary to any of the miRNAs disclosed in the Tables).
  • the isolated nucleic acid molecule can comprise a sequence of one or more RT-PCR target sequences, primers directed thereto, or a sequence complementary thereto.
  • the kit can also include adapter nucleic acid molecules (e.g., universal adapter molecules for attachment to expressed miRNAs/mRNAs for reverse transcription and amplification); appropriate buffer systems and reagents, detectable labels, an energy source (e.g., ATP), and other agents and components that can be used in performing analysis of miRNA expression (e.g., in RT-PCR, deep sequencing, or microarray-based methods). Kits also include instructions for use.
  • adapter nucleic acid molecules e.g., universal adapter molecules for attachment to expressed miRNAs/mRNAs for reverse transcription and amplification
  • detectable labels e.g., an energy source (e.g., ATP), and other agents and components that can be used in performing analysis of miRNA expression (e.g., in RT-PCR, deep sequencing, or microarray-based methods).
  • Kits also include instructions for use.
  • any numerical value recited herein includes all values from the lower value to the upper value. For example, if a concentration range is stated as 1% to 50%, it is intended that values such as 2% to 40%, 10% to 30%, or 1% to 3%, etc., are expressly enumerated in this specification. These are only examples of what is specifically intended, and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application.
  • the disclosure provides a DNA library comprising one or more miRNA sequences from Tables 4-5, or 6-33. In a related aspect, the disclosure provides a method for generating such a DNA library.
  • the library comprises a cDNA library that includes sequences derived from a sample of the miRNAs or, in addition or alternatively, the mRNA purified from a particular source such as, for example, a collection of cells, a particular tissue, or an entire organism.
  • the source of the cDNA library is a B cell, such as a B cell in any stage (e.g., na ⁇ ve, germinal center, memory, activated, or plasma, etc.) or a B cell malignancy (e.g., mantle cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, germinal center B-cell like diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, and activated B-cell like DLBCL).
  • a B cell malignancy e.g., mantle cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, germinal center B-cell like diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia, small
  • the isolated miRNA (or mRNA) is converted to a DNA template by reverse transcription, and comprises the cDNA version of the expressed RNA (e.g., miRNA or mRNA).
  • a library can represent the cDNA version of the active “transcriptome” in a particular source under the physiological, developmental, or environmental conditions that existed when the miRNA/mRNA was purified.
  • the library comprises a miRNA sequence described in Tables 4-5; 7-33. In embodiments, the library comprises at least one of SEQ ID NOs 763-1350 or 1565, and any combination thereof. In an embodiment, the library comprises a collection of miRNA sequences comprising SEQ ID NOs 763-1350 or 1565. In embodiments the library can be used to identify and/or differentiate a B-cell malignancy from other B-cell malignancies. In such embodiments, the library comprises at least one miRNA sequence selected from those listed in any of Tables 4 or 7-35.
  • a “library” is a collection of DNA sequences that is stored and propagated in a population of microorganisms through standard molecular cloning processes.
  • a DNA library can be of any type such as, for example, a cDNA library (formed from reverse-transcribed RNA) or a genomic library (formed from genomic DNA).
  • the DNA library can be used in any routine application or technique known in the art (e.g., gene discovery; cloning of full-length cDNAs to identify/study gene function; miRNA/mRNA expression in different cells or tissues; splice variants in different cells or tissues) and, in some embodiments, can depend on the source of the original DNA fragments.
  • the library can be used to isolate, characterize, and/or quantify the actively expressed miRNA is a population of cells such as, for example, B-cells or B-cell malignancies.
  • the library can be used to study miRNA-protein interactions or miRNA-based regulation of protein expression or activity.
  • RNA Methodologies A Laboratory Guide for Isolation and Characterization (R. E. Farrell, Academic Press, 1998); cDNA Library Protocols (Cowell & Austin, eds., Humana Press; Functional Genomics (Hunt & Livesey, eds., 2000); and the Annual Review of Genomics and Human Genetics (E. Lander, ed., yearly publications by Annual Reviews).
  • the nucleotide sequences of interest in a library are preserved as inserts in a plasmid or the genome of a bacteriophage that has been used to infect bacterial cells.
  • cloning vectors and techniques used in library preparation differ in the cloning vectors and techniques used in library preparation, but in general each DNA fragment is uniquely inserted into a cloning vector and the pool of recombinant DNA molecules is then transferred into a population of bacteria or yeast such that each organism contains on average one construct (vector+insert).
  • the DNA molecules are copied and propagated along with the population of organisms in culture (thus, effectively, “cloned”).
  • the term “library” can refer to a population of organisms, each of which carries a DNA molecule inserted into a cloning vector, or alternatively to the collection of all of the cloned vector molecules.
  • an “increased level” of expression refers to a level of expression that is at least 2-fold greater than the level of expression in a control cell type or tissue.
  • the level of expression is at least 2.5-fold, at least 3-fold, at least 5-fold, or at least 10-fold, greater than the level of expression in a control cell.
  • Exemplary control cells and tissues include, but are not limited to, normal cells, benign lymph nodes, and other B cell malignancies.
  • benign lymph nodes are used as a control tissue. Such benign lymph node tissue contains a variety of cell types.
  • a “decreased level” of expression refers to a level of expression that is less than 50% of the level of expression in a control cell.
  • differentiated or “differential expression” relates to a difference in the observed or detected level of expression of a biomolecule such as, for example, nucleic acids (e.g., a polynucleotide, mRNA, miRNA, etc.) or amino acid sequence (e.g., protein, polypeptide, etc.) in a test sample relative to the observed or detected level of expression of the same biomolecule in a control sample or other reference (e.g., a previously established reference level).
  • the difference in expression can be either an increase or a decrease in the expression of the biomolecule in the test sample relative to the control sample.
  • B cell populations were obtained from young patients undergoing routine tonsillectomy using a protocol approved by the Clinical Center at the National Institutes of Health. Patient tonsils were disaggregated and separated by Ficoll. The mononuclear cell layer was harvested, washed in PBS, and resuspended in ACK lysing buffer to remove small numbers of red blood cells. After a wash and resuspension with 10 ml of PBS with 10% Bovine Serum Albumin, cells were counted and 200 million were stained with fluorochrome-tagged monoclonal antibodies to CDI9, IgD, CD38 and CD27.
  • the specific monoclonal antibodies employed were anti-CDI9-PE-Cy5.5, anti-IgD-FITC, anti-CD27-PE, and anti-CD38-APC, all from BD Biosciences and BD Pharmingen (San Jose Calif.).
  • Cells were sorted using the MoFlo Cell sorter (Dako Cytomation, Colorado Springs, Colo.) into naive B cells (CDI9+IgD+CD2TCD38+), germinal center B cells (CDI9+IgD ⁇ CD38++), memory B cells (CDI9+IgD ⁇ CD27+CD38dim) and plasma cells (CDI9dimIgD ⁇ CD27++CD38+++).
  • naive B cells CDI9+IgD+CD2TCD38+
  • germinal center B cells CDI9+IgD ⁇ CD38++
  • memory B cells CDI9+IgD ⁇ CD27+CD38dim
  • plasma cells CDI9dimIgD ⁇ CD27
  • MiRNA expression profiling was conducted using the Applied Biosystems 384-well multiplexed real-time PCR assay using 400 ng of total RNA. Eight reactions, each containing 50 ng of RNA and a multiplex looped primer pool with endogenous small nucleolar (sno)-RNA controls, were used to reverse-transcribe the miRNAs in parallel fashion. Each completed reaction was loaded onto the 384-well plate per manufacturer's instructions, and real-time PCR was run on the ABI 7900HT Prism. For each 384-well plate, we used the automatically determined cycle-threshold (CT) using the SDS 2.2.1 software (Applied Biosystems). Consistent with manufacturer recommendations, we considered CT greater than 36 as undetected.
  • CT cycle-threshold
  • a miRNA was considered to be present in a subpopulation if the CT was less than 36 in all three biological replicates.
  • the probes deemed to be present were normalized to the average expression of a sno-RNA control.
  • the expression values were calculated as 2 ⁇ CT , then median centered to 500 and log 2-transformed.
  • MiRNA expression profiling from human B cell malignancies was conducted using up to 1 ⁇ g of total RNA from sample and reference (normal lymph node), which were labeled with Cy3 or Cy5 fluorescent dyes, using the miRNA/LNA labeling kit (Exiqon, Denmark).
  • the fluorescently labeled samples were combined and hybridized to a miRNA microarray (v.10.0, Exiqon, Denmark), in a nitrogen atmosphere.
  • the micro array slides were scanned with GenePix 4100 Scanner.
  • the quantified signals were normalized using the global Lowess algorithm, using Genespring (Agilent) software.
  • the intensity values for multiple spots were averaged and the normalized values were log 2-transformed. Missing values were replaced with the lowest value for analysis.
  • TargetScan www.targetscan.org
  • a target gene was defined by the presence of a seed sequence match (nucleotides 2-8) and conservation of the seed sequence and 3 ′UTR in humans, dog, rat, mouse and chicken. Additional conservation was examined in miRNA target genes selected for experimental validation. The distribution of the mRNA expression for these genes was plotted as a density plot using the Splus statistical software (Insightful Corporation).
  • the difference in distribution between the B cell subsets was calculated using a two-sample, 1-sided Kolmogorov-Smirnov test to examine the hypothesis that being a miRNA target conferred repression in the appropriate population (consistent with the known biology of miRNA effects).
  • the 3′UTRs of LM02, MYBL1 and PRDM1 were aligned using Blastz alignment of Human, Chimp, Mouse, Rat, Dog, Chicken, Frog (Xenopus) and Zebrafish, and were displayed using the UCSC genome browser. The conservation of miR-223 seed sequence and the 3′UTRs of LM02 and MYBL1, as well as that of the miR-30 family and miR-9 on PRDM1, were thus verified.
  • RIPA Lysis buffer (1 ⁇ phosphate-buffered saline [PBS], 1 Nonidet P-40, 0.5% sodium deoxycholate, 0.1% SDS, 10 mM phenylmethylsulfonyl fluoride, 1 ⁇ g/mL aprotinin, and 100 mM sodium orthovanadate) was added to 750,000 cells and incubated on ice for 30 minutes. The mixture was spun down and the supernatant was transferred to a new tube as the whole cell extract.
  • PBS phosphate-buffered saline
  • SDS sodium deoxycholate
  • 10 mM phenylmethylsulfonyl fluoride 1 ⁇ g/mL aprotinin
  • 100 mM sodium orthovanadate 100 mM sodium orthovanadate
  • a total of 20 ⁇ g of cell lysate was separated on a 4-18% Tris-Bis NuPAGE gel (Invitrogen) and transferred using the iBlot transfer device (Invitrogen) program 3 for 7 minutes (LM02 detection) or program 2 for 6 minutes (PRDM1).
  • the blots were probed using 1:200 mouse-anti-LM02 (Santa Cruz Biotechnologies SC-65736), 1:750 mouse-anti-Blimp-1 (Santa Cruz Biotechnologies SC-66015) or 1:5000 goat-anti-B-actin (Santa Cruz Biotechnologies SC-47778) for 1 hour at room temperature.
  • the antibodies were detected using 1:10,000 goat-anti-mouse horseradish peroxidase conjugated antibodies (Santa Cruz Biotechnologies).
  • Western Blotting Luminol Reagent (Santa Cruz Biotechnologies) was used to visualize the bands corresponding to each antibody.
  • RT-PCR Real-Time Polymerase Chain Reaction
  • RNA was reverse-transcribed with ABI individual stem-loop primers designed to detect only mature miRNA, and measured by Taqman real-time PCR normalized to the small nucleolar RNA, RNU48.
  • ABI High Capacity cDNA Reverse Transcription kit was used to assess mRNA expression using RT-PCR. Gene expression was measured with exon-spanning Taqman probes, and normalized to beta-2 micro globulin expression.
  • BJAB and H929 were cultured in RPMI (Gibco) supplemented with 10% fetal bovine serum, and U266 was cultured in RPMI supplemented with 15% fetal bovine serum.
  • 293T cells were grown in DMEM media (Gibco) with 10% FBS. All cell lines were grown in 37° C. humidified cell culture incubators with CO 2 maintained at 5%.
  • miRNAs of interest were over-expressed in cell lines of interest by transfecting the appropriate miRNA precursors (Ambion) at 100 nanomoles using Amaxa's Nucleofector system.
  • BJAB was transfected with Nucleofector solution T, program T-016, U266 with Nucleofector C, program X-005, and H929 with Nucleofector V, program T-001. 1.5 million cells were used per transfection and mixed with appropriate miRNA precursors (Ambion) for a concentration of 100 nM.
  • MiRNAs were considered to be differentially expressed if the mean signal was changed at least 2-fold and a false discovery rate (q) was less than 5% using Significance Analysis of Microarrays (SAM) with 1000 permutations. See Tusher et al. Proc Natl Acad Sci USA. 2001; 98:5116-5121.
  • SAM Significance Analysis of Microarrays
  • mRNA Differentially expressed genes in Naive versus Germinal Center, Germinal Center versus Plasma Cells, and Germinal Center versus Memory Cells comparisons were identified using SAM. Genes that were 2-fold differentially expressed at a false discovery rate (q) less than 1% with 1000 permutations were identified as significantly differentially expressed.
  • Transcription factors were identified based on the gene ontology (GO search term “transcription factor”) and matched to the probes of the Affymetrix U133plus 2.0 microarray. Of the total of 938 transcription factor genes thus identified, we selected 364 genes that were differentially expressed in at least one of the B cell stage transitions. We evaluated the breakdown of the differentially expressed transcription factors among miRNA targets versus non targets. The p-values were computed using a chi-square test separately in each B cell stage-transition.
  • the top 50 most differentially expressed miRNAs (P ⁇ 0.01) in each pair-wise B cell malignancy type comparison were chosen as the initial predictor. Singular value decomposition was applied to reduce the list to 20 most informative miRNAs in each pair-wise comparison. See West et al. Proc Natl Acad Sci USA. 2001; 98:11462-11467. A Bayesian logistic regression was performed in Matlab (Mathworks) using the 20-predictor miRNAs for each pair-wise comparison. Each sample was tested using the microRNA-based predictor in a leave-one-out fashion to determine the accuracy of each prediction. For a sample to be classified as a particular B cell malignancy (or normal) type, it had to be predicted as such in every pair-wise comparison.
  • Firefly luciferase reporter constructs were created in the pL/SV40/GL3 vector for the LM02 3′UTR and the LM02 3′UTR with the predicted miR-223 binding site mutated, as described below.
  • Mature microRNA expression of a pL/CMV/eGFP vector coding for pri-miR-223 from the 3′UTR of EGFP of the vector was confirmed by Taqman-real time PCR in transfected 293T cells. gl3 activity was normalized in dual luciferase assays to pL/SV40/RLuc, with which it was cotransfected.
  • the PRDM1 3′UTR was also cloned into the pL/SV40/GL3 vector.
  • microRNA expression vectors and their respective seed sequence mutants were created for miR-9-2, miR-30b, and miR-30d.
  • the LM02 3′UTR was PCR-amplified from BJAB cDNA using primers 1 and 2 (SEQ ID NOs: 1 and 2, respectively) and ligated into the XhoI and XbaI sites of the previously described lentiviral vector pL/SV40/GL3, which expresses firefly luciferase. See Tusher et al. Proc Natl Acad Sci USA. 2001; 98:5116-5121.
  • an LM02 3′UTR mutant was created using mutant PCR primers 3 and 4 and then outer primers 1 and 2. The resulting fragment was also placed into the XhoI and XbaI sites of pL/SV40/GL3.
  • the seed match predicted to bind to nucleotides 2-8 of miR-223 is converted from 5′AACUGAC 3′ to 5′AACAGUC 3′.
  • a miR-223 expression vector a ⁇ 350 nucleotide-long fragment of pri-miR-223, encompassing the pre-miRNA stem loop in its middle, was PCR-amplified from genomic BJAB DNA with primers 6 and 7 (SEQ ID NOs. 6 and 7) and ligated into the XhoI and XbaI sites of the pL/CMV/eGFP vector.
  • This pL/CMV/eGFP vector was generated by ligating a fragment containing the CMV promoter and the EGFP ORF into the BamHI and XhoI sites of the previously described lentiviral backbone pL. See Tusher et al. Proc Natl Acad Sci USA. 2001; 98:5116-5121. The expression of miR-223 from the 3′UTR of EGFP in the resulting vector was confirmed by Taqman real time PCR in transfected 293T cells.
  • Luciferase indicator assay compositions 2.5 ng pL/SV40/GL3 2.5 ng pL/SV40/GL3/ 2.5 ng pL/SV40/GL3/ 2.5 ng pL/SV40/RLuc LMO2 LMO2 seed 0.4 ⁇ g pL/CMV/ UTR mut eGFP/miR-223 2.5 ng pL/SV40/RLuc 2.5 ng pL/SV40/RLuc 2.5 ng pL/SV40/GL3 0.4 ⁇ g pL/CMV/ 0.4 ⁇ g pL/CMV/eGFP/ 2.5 ng pL/SV40/RLuc eGFP/miR-223 miR-223 0.4 ⁇ g pL/CMV/eGFP 2.5 ng pL/SV40/ 2.5 ng pL/SV40/GL3/ GL3/LMO2 LMO2 seed UTR mut 2.5 ng pL/SV40/RLuc 2.5 ng pL/SV40/
  • Reporter expression was evaluated by dual luciferase assays (Promega) 48 hours post-transfection.
  • Firefly Luciferase (GL3) to internal control Renilla Luciferase (RLuc) ratios from 293T cells transfected with pL/CMV/eGFP/miR-223 were divided by those obtained from 293T transfected with the pL/CMV/eGFP vector control.
  • the average and standard deviation were taken across five experiments for the pL/SV40/gl3 empty, LM02, and LM02 mutant vectors.
  • Firefly Luciferase (GL3) activity readings of the PRDM1 3′UTR construct were divided by internal control Renilla Luciferase (RLuc) activity readings. The average and standard deviation of these ratios across three experiments were calculated and scaled relative to the empty vector (pL/CMV/eGFP) transfection.
  • the PRDM1 3′UTR was PCR-amplified from BJAB genomic DNA in two reactions using primer pairs 7 and 8 in one reaction, and 9 and 10 in another (SEQ ID NOs: 7 to 10, respectively). The two fragments were then ligated together into the XhoI and NotI sites of pL/SV40/GL3 to generate the entire PRDM1 3′UTR.
  • microRNA expression vectors were created as described above for mir-9-2, mir-30b, and mir-30d with the primers listed below. Again, over-expression from the 3′UTR of EGFP in the resulting vector was confirmed by Taqman real-time PCR in transfected 293T cells.
  • PRDM1 primer sequences Primer SEQ ID: description sequence 1549 PRDM1 3′UTR piece 1, FW AGAGACTCGAGGATTTTCAGAAAACACTTATTT 1550 PRDM1 3′UTR piece 1, REV TTGCTTCTCTAGAGGAGAAAC 1551 PRDM1 3′UTR piece 2, FW GTTTCTCCTCTAGAGAAGCAA 1552 PRDM1 3′UTR piece 2, REV AGAGAGCGGCCGCAGGGGAGAGACAAATTGCATTG 1553 pri-mir-9-2, FW AGAGACTCGAGATAAAAGGAGGAATCTTAAG 1554 pri-mir-9-2, REV AGAGAGCGGCCGCGCGAAAAACAAAACAAAAACAA 1555 pri-mir-30b, FW AGAGAGCGGCCGCCCGATTGAGTCTTGCCTCAT 1556 pri-mir-30b, REV AGAGAATTCAATGGTCTCACATTTCCAAC 1557 pri-mir-30d, FW AGAGAGCGGCCGCATGTCACAGCTATT
  • Luciferase assays were carried out in a manner similar to those described for LMO2.
  • genomic DNA was isolated from purified CLL cells and isolated using the GenElute Mammalian DNA extraction Kit from Sigma (St. Louis, Mo.) according to the manufacturer's instructions. DNA was amplified using nested PCR primers. PCR products were electrophoresed, purified, and sequenced using an automated DNA sequencer (Applied Biosystems, Foster City, Calif.) with the BigDye Terminator kit (Perkin Elmer, Boston, Mass.).
  • Mature B cell subsets can be defined by the expression of surface CD19, IgD, CD38, and CD27, and were obtained by fluorescence activated cell sorting of tonsils from young individuals undergoing routine tonsillectomy. See FIGS. 1B and 1C . Cells were previously gated on CD19 positive cells. Naive and memory B cells were distinguished from germinal center and plasma cells based on surface CD38 and IgD expression.
  • RNA microRNA
  • RT-PCR real time polymerase chain reaction
  • the B cell subsets were profiled for gene expression at the whole genome level, as described previously. See Dave et al. N Engl J Med. 2004; 351:2159-2169. At each stage, we identified differentially expressed genes as those genes with a mean two-fold difference in expression and a false-discovery rate of less than 1%. See FIGS. 1E , 1 G, and 1 I. Genes that we found to be differentially expressed in each stage-transition were consistent with previous studies that examined gene expression in B cell subsets using microarrays with fewer probes, an overlap that was found to be highly statistically significant (P ⁇ 0.001, chi-squared test). See, e.g., Klein et al. Proc Natl Acad Sci USA. 2003; 100:2639-2644; and Shaffer et al. Immunity. 2001; 15: 375-385.
  • GC na ⁇ ve ⁇ germinal center
  • the expression pattern of all the miRNAs that were measurable in at least one of the B cell subsets is summarized in FIG. 5 . Notably, there were no differences in the expression of genes involved in miRNA processing, including DICER1, DROSHA, XP05 (exportin5), EIF2C2 (ag02) and DGCR8, among the B cell subsets. See FIG. 1J .
  • FIG. 6A shows density plots of the expression frequency of predicted mRNA targets of microRNAs expressed highly in germinal center B cells compared to naive cells.
  • FIG. 6B shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in germinal center B cells compared to plasma cells.
  • the depicted p-value was calculated using a 1-sided Kolmogorov-Smirnov test.
  • FIG. 6C shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in the germinal center B cells compared to memory B cells.
  • the depicted p-value was calculated using a 1-sided Kolmogorov-Smirnov test.
  • genes with at least a two-fold change in expression were analyzed by SAM using a false discovery rate of less than 1% (Larsson et. al, BMC Bioinformatics. 2005; 6:129), depicted in FIG. 1E .
  • FIG. 1E From that list of significantly differentially expressed genes, we determined those that were predicted targets of miRNAs (defined as genes with 3′UTR sequence complementarity to microRNA nucleotides 2-7) that were expressed more highly in germinal center cells.
  • the gene expression distribution of those mRNA targets was graphed for na ⁇ ve B Cells (blue curve) and germinal center B cells (orange curve).
  • MiR-223 Regulates LM02 in the Naive ⁇ Germinal Center and Germinal Center ⁇ Memory Cell Transitions
  • MiR-223 has previously been described as being important in the commitment to myeloid lineage. See Chen et al. Science. 2004; 303:83-86; Johnnidis et al. Nature. 2008; 451:1125-1129. We found miR-223 to be expressed at nearly 8-fold higher levels in both naive and memory cells compared to GC cells. This miRNA has a highly conserved sequence complementarity to the 3 ′UTR of 2 transcription factors that are expressed highly during GC cell differentiation: LM02 ( FIG. 2A ) and MYBL1 ( FIG. 8A ). Higher expression of miR-223 in the naive B cell stage could inhibit the untimely expression of these transcription factors until the cell is ready to undergo the germinal center reaction.
  • LM02 The expression of LM02 was consistently lower in the cells treated with the miR-223 precursor, and the results were statistically significant (P ⁇ 0.05 in all cases, student's t-test). There was no effect on the expression of a non-target control, beta-2 micro globulin in these experiments (data not shown).
  • Over-expression of miR-223 also resulted in a consistent down-regulation of LM02 at the protein level compared to a transfection with a scrambled control with no sequence complementarity to the human genome. See FIG. 2C .
  • FIG. 2D We quantified the results of 3 separate experiments examining LM02 protein expression and found consistent down-regulation of LM02 in cells treated with miR-223 compared to cells transfected with scrambled controls. See FIG. 2D .
  • LM02 Activation of LM02 has been associated with the development of leukemia in patients undergoing gene therapy. Hacein-Bey-Abina et al. Science. 2003; 302:415-419. On the other hand, higher expression of PRDM1 alone is sufficient to induce plasma cell-differentiation. Turner et al. Cell. 1994; 77:297-306. Inappropriate expression of such genes must be effectively turned off for a cell to maintain its state. This mode of regulation is reflected in the effects of miR-223, miR-9 and miR-30, which turn off the inappropriate expression of LM02 and PRDM1 and might promote state maintenance and inhibition of lymphomagenesis.
  • the transcription factor PRDM1 is an essential regulator of plasma cell differentiation. Martins et al. Annu Rev Immunol. 2008; 26:133-169.
  • the miR-30 family comprises 5 members (miR-30a, 30b, 30c, 30d and 30e), of which 4 (all except 30e) were found to be expressed at higher levels in GC cells compared to plasma cells.
  • Control transfection experiments documented good specificity of the RT-PCR probes for individual members of the miR-30 family with no discernible cross-hybridization. See FIG. 9 . Three separate transfection experiments using high concentrations of miR-30b precursors are shown in the left panel with measurement of miR-30b and miR-30d. Similar experiments were performed with precursors for miR-30d (right panel).
  • the 3′UTR of PRDM1 contains 3 highly conserved binding sites complementary to the seed sequence of members of the miR-30 family, as well as 3 binding sites for the seed sequence of miR-9, 2 of which are highly conserved across multiple species. See FIG. 3A .
  • the 3′UTR region of PRDM1 complementary to miR-30 is shown in red.
  • the 3 sites are complementary to nucleotides 2-8 (UTR position 408), nucleotides 1-8 (UTR position 2370) and nucleotides 2-8 (UTR position 2383) on the miRNA, respectively.
  • the 3′UTR region of PRDM1 complementary to miR-9 is shown in green.
  • the 3 sites are complementary to nucleotides 1-7 (UTR position 1459), nucleotides 2-8 (UTR position 2108) and nucleotides 2-8 (UTR position 2323) on the miRNA respectively. These sites are highly conserved across a number of species, with the exception of one miR-9 site (UTR position 1459) that is only present in humans.
  • the magenta bars depict the expression of PRDM1 24 hours after transfection with a hairpin precursor for miR-30b, while the red bars depict the expression of PRDM1 24 hours after transfection with a hairpin precursor for miR-30d.
  • the green bars depict the expression of PRDM1 24 hours after transfection with a hairpin precursor for miR-9.
  • luciferase reporter activity of the PRDM1 3′UTR construct was decreased by overexpression of miR-9, miR-30b, and miR-30d, but not their respective seed sequence mutants. See FIG. 3E , which shows the average of three experiments.
  • the down-regulation of the luciferase reporter signal and its restoration in the mutant constructs was found to be statistically significant in each of the 3 microRNAs: miR-9, miR-30b and miR-30d (P ⁇ 0.05, student's t-test).
  • the luciferase reporter activity level was rescued to the activity level of the empty vector control when the seed sequence of the microRNAs was mutated.
  • microRNAs The combined effect of 5 different microRNA species (miR-30a, miR-30b, miR-30c, miR-30d and miR-9) is likely to be more potent than that of a single microRNA.
  • miRNA expression may promote a highly regulated state that enables GC cells to interact with T cells and antigen presenting cells, and to leave the GC cells poised for differentiation into memory or plasma cells.
  • miRNAs expressed highly in naive and plasma cells may be underrepresented in current miRNA libraries. Such libraries are often constructed from lymph nodes, which are typically enriched in GC cells. High throughput sequencing of sorted populations of B cells could reveal novel miRNAs that are highly expressed in those populations. Interestingly, a larger number of miRNAs were highly expressed in memory cells compared to GC cells. This observation might stem from the fact that memory cells are known to be heterogeneous (Sanz et al. Semin Immunol. 2008; 20:67-82) and standard methods used to select memory cells may capture a diverse group of memory subpopulations.
  • FIG. 1H We constructed a Bayesian predictor from miRNAs that distinguished normal memory B cells from GC cells. See FIG. 1H .
  • MicroRNA profiling also revealed that each B cell malignancy type had a distinctive pattern of miRNA expression. See FIG. 4D .
  • Bayesian predictors from the most highly differentially expressed miRNAs for each pair-wise comparison. See Tables 7, 8, and 9.
  • GCBvsBL GCBvsABC GCBvsCLL hsa-miR-146a hsa-miR-142-3p hsa-miR-126 hsa-miR-154 hsa-miR-16 hsa-miR-130a hsa-miR-155 hsa-miR-184 hsa-miR-I0b hsa-miR-184 hsa-miR-191 hsa-miR-154 hsa-miR-29b hsa-miR-19a hsa-miR-193b hsa-miR-29c hsa-miR-19b
  • microRNAs that can be used to distinguish each of the six B cell malignancies analyzed from the other five. Lists of those microRNAs, and whether they are expressed in high levels or low levels relative to the other 5 B cell malignancies, are shown in Tables 10 through 13. In certain embodiments, each of those microRNAs could be used to distinguish one of the six B cell malignancies from the other five. High and low in the table refer to at least a 2 fold difference when compared to other lymphomas and benign lymph nodes.
  • microRNAs From the data in Tables 10 through 13, we identified subsets of microRNAs that are sufficient to distinguish each of the six B cell malignancies from the other five. We selected only microRNAs that are expressed more highly in the selected B cell malignancy. Those microRNAs are listed in Tables 14 and 15. In certain embodiments, each of the microRNAs listed in Tables 14 and 15 can be used to distinguish one B cell malignancy from the other five.
  • microRNAs that can distinguish between each pair of B cell malignancies in the study. Lists of those microRNAs are shown in Appendix B, Tables 16 to 30. In certain embodiments, each of the listed microRNAs is sufficient to distinguish between the two B cell malignancies listed in the table description.
  • stage-specific B cell markers such as BCL6, a marker for GC cells
  • BCL6 a marker for GC cells
  • stage-specific biology in B cell malignancies is retained at the miRNA level.
  • Recent work has demonstrated the utility of gene expression profiling in reliably distinguishing closely related B cell malignancies. See Hummel et al. N Engl J Med. 2006; 354:2419-2430; Dave et al. N Engl J Med. 2006; 354:2431-2442.
  • clinical translation of gene expression profiling has proved to be difficult because of the need for freshly frozen tissue.
  • miRNAs can be isolated from tissues preserved using standard methods (see, e.g., Doleshal et al. J Mol Diagn. 2008; 10:203-211; Xi et al. Rna. 2007; 13:1668-1674), diagnostic methods based upon miRNA profiles could be fairly easy to translate to clinical use.
  • Diffuse large B cell lymphoma is the most common form of lymphoma and is known to comprise at least 2 molecularly distinct subgroups with different responses to standard therapy. These two distinct subgroups are typically identified as ABC DLBCL and GC (or GCB) DLBCL.
  • Total RNA was extracted from the 31 samples using the phenol-chloroform method to preserve microRNAs, using Ambion reagents.
  • Total RNA typically 5 ⁇ g
  • the ⁇ 17-25 nucleotide RNAs were excised from the gel, ligated to sequencing adaptors on both ends and reverse transcribed.
  • the resulting cDNA library was PCR-amplified for 15 cycles and gel purified on 6% acrylamide gel. The gel-purified amplicon quality and quantity were analyzed on a 6% acrylamide gel relative to oligonucleotides of known concentration and size.
  • RNA libraries from the 31 samples which were subjected to massively parallel, high-throughput sequencing using the Illumina platform generated a total of 328 million separate reads.
  • Our approach to analyzing the sequences and discovering microRNAs broadly follows a previously described method (see, Zheng, Q., et al. GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis, Nucleic acids Res. 2008; 36 (Web Server issue: W358-363). All bioinformatics analyses were performed using a cluster of 1024 Linux computer nodes. Preprocessing was carried out using locally written Shell and Perl scripts.
  • Genomic loci that overlapped with microRNAs described in miRBase were identified as known microRNAs (see Table 31). The remaining genomic loci were identified as encoding candidate novel microRNAs (see Table 32).
  • microRNAs The vast majority (96%) of the candidate novel microRNAs were found in more than one sample, with only a small minority of microRNAs were expressed exclusively in a specific B cell subset or malignancy. Many of the microRNAs that we identified in normal and malignant B cells were expressed at ten-fold or higher levels in these non B cell cases.
  • miRNA expression profiling was conducted using the Applied Biosystems 384-well multiplexed real-time PCR assay using 400 ng of total RNA. Eight reactions, each containing 50 ng of RNA and a multiplex looped primer pool with endogenous small nucleolar (sno)-RNA controls, were used to reverse-transcribe the miRNAs in parallel fashion (see Tables 33 and 34 for primers). The completed reactions were loaded onto the 384-well plate per manufacturer's instructions, and real-time PCR was run on the ABI 7900HT Prism instrument. For each 384-well plate, we used the automatically determined cycle-threshold (C T ) using the SDS 2.2.1 software (Applied Biosystems).
  • C T cycle-threshold
  • Tumor samples from 101 patients with diffuse large B cell lymphoma were obtained at the time of diagnosis and freshly frozen. These cases were profiled using Affymetrix Gene 1.0 ST arrays. The molecular subgroups were distinguished using a Bayesian approach described previously (Ambros, V., et al., RNA (2003);9(3):277-279).
  • microRNAs that we have identified in our study may be expressed at higher levels in other development stages or in other cell types. This notion is confirmed by our examination of the novel microRNAs in non B cell data. For instance, a number of the microRNAs that we discovered were also present at 10-fold or higher levels in cell lines derived from breast cancer and cervical cancer, suggesting that the microRNAs that we have discovered in B cells have broad biological significance.
  • microRNAs appear to be distributed throughout the genome, a number of microRNAs have been found in clusters such as miR-17-92 that are transcribed from a single primary transcript and cleaved into the individual microRNAs by the enzyme DROSHA.
  • clusters such as miR-17-92 that are transcribed from a single primary transcript and cleaved into the individual microRNAs by the enzyme DROSHA.
  • the first cluster was previously annotated as a hypothetical gene LOC100130622, and subsequently discarded from Refseq when no associated protein was identified.
  • microRNA processing enzyme Drosha acts at the first step of microRNA processing by cleaving microRNA precursors from the primary transcript.
  • Drosha expression was associated with increased accumulation of primary transcripts of both the miR-17-92 cluster as well as the novel miR-2355 cluster.
  • MicroRNAs from miR-2355 cluster were found to be expressed more highly in normal germinal center (GC) B cells compared to memory cells.
  • microRNAs of this cluster all share the same seed sequence, suggesting that they target the same genes.
  • SMAD2 and SMAD3 which are well known mediators of the TGF-beta signaling pathway.
  • gene expression of both SMAD2 and SMAD3 in our set of 101 DLBCLs were inversely correlated with this cluster (P ⁇ 0.001, correlation test).
  • Gene set enrichment analysis revealed that expression of the TGF-beta pathway in DLBCL samples varied inversely with the expression of the microRNA cluster, with a higher expression of the microRNA associated with a lower expression of the pathway (P ⁇ 10 ⁇ 6 ), which has been noted as a factor in the biology of these tumors.

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Abstract

Disclosed are nucleic acid sequences, including microRNA sequences and cDNA sequences, as well as vectors, DNA libraries, microarrays, and recombinant cells comprising the nucleic acid sequences described herein. Methods of determining the B cell stage from which a B cell malignancy is derived. Methods of identifying B cell malignancies are also provided. Methods of diagnosing B cell malignancies are provided. Such methods comprise, in certain embodiments, detecting one or more microRNAs or cDNAs as disclosed herein.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application is related to and claims the benefit of priority of U.S. Provisional Application Ser. No. 61/266,733, filed Dec. 4, 2009, which is incorporated herein by, reference.
  • STATEMENT OF GOVERNMENT SUPPORT
  • This invention was made with United States government support from the National Institutes of Health grant no. K12-CA-100639. The United States government has certain rights in this invention.
  • SEQUENCE LISTING
  • The sequence listing is filed with the application in electronic format only and is incorporated by reference herein. The sequence listing text file “WO_ASFILED_SequenceListing.txt” was created on Dec. 3, 2010, and is 262,254 bytes in size.
  • BACKGROUND
  • Naive B cells migrate through the circulation to lymphoid organs where they undergo the T cell-dependent germinal center reaction. Adaptive immunity is acquired as specific antigen-reactive germinal center B cells differentiate into the major effector B cells of the adaptive immune system: memory cells and plasma cells. See, e.g., FIG. 1A. Although the role of specific transcription factors in mature B cell differentiation has been examined (see Nutt et al. Nature. 1999; 401:556-562; Chang et al. Proc Natl Acad Sci USA. 1996; 93:6947-6952; Turner et al. Cell. 1994; 77:297-306; Shaffer et al., Immunity. 2004; 21:81-93; and Schebesta et al. Curr Opin Immunol. 2002; 14:216-223), mechanisms regulating such transcription factors during mature B cell differentiation are largely unknown.
  • Many malignancies derived from mature B cells are known and are believed to constitute the majority of leukemias and lymphomas. Such malignancies appear to reflect defined stages of normal B cell differentiation. Diagnosis of leukemias and lymphomas can be particularly difficult because of their shared lineage. These cancers frequently display overlapping morphologies, genetic abnormalities, and expression of surface markers, which can complicate the diagnosis. However, the distinction of these tumors is clinically important because there are important differences in the treatments and expected response to treatment. Thus methods that improve the accuracy of their diagnosis should provide to improved outcomes for these patients.
  • MicroRNAs are commonly 18-22 nucleotide-long RNA molecules that regulate expression of genes. There is an increasing recognition of the role of microRNAs in oncogenesis, lineage-selection, and immune cell function, including early B cell differentiation. See Calin et al. N Engl J Med. 2005; 353:1793-1801; O'Donnell et al. Nature. 2005; 435:839-843; Chen et al. Science. 2004; 303:83-86; Lim et al. Nature. 2005; 433:769-773; Li et al. Cell. 2007; 129:147-161; Xiao et al., Nat Immunol. 2008; 9:405-414; Baltimore et al. Nat Immunol. 2008; 9:839-845; and Ventura et al. Cell. 2008; 132:875-886. However, the full extent and function of microRNA expression during mature B cell differentiation and in B cell malignancies are not known.
  • Correct diagnosis of B cell malignancies is important from both a clinical standpoint and from the standpoint of setting appropriate patient expectations. A misdiagnosed B cell malignancy may lead to an inappropriate therapy, which can unnecessarily endanger the patient's life and/or be an ineffective treatment for the B cell malignancy. As an example, the diagnostic distinction of Burkitt lymphoma (BL) from diffuse large B cell lymphomas (DLBCLs) can be difficult because of overlapping morphology, immunophenotype and cytogenetics. Burkitt lymphoma tumors are molecularly distinct from DLBCL, however. The difficulty and importance of obtaining the correct diagnosis in BL was highlighted by the experience of a multicenter clinical trial, CALGB trial#925119, in which nearly half of the 100 patients with an assigned diagnosis of BL were found to have another diagnosis upon further pathology review.
  • If diagnosed and treated appropriately, nearly 80% of patients with BL can be cured with intensive (high dose) chemotherapy regimens. Thus, a misclassification of BL as DLBCL can result in a missed opportunity to cure the malignancy. On the other hand, misclassification of DLBCL as BL leads to unnecessarily morbidity from intensive chemotherapy regimens. Thus, methods that improve the diagnosis of BL, and other B cell malignancies, can provide better outcomes in patients.
  • DLBCLs can also be subclassified into two different B cell malignancies, activated B-cell (ABC) DLBCL and germinal center B cell like (GCB) DLBCL. There are at least two important clinical applications for the molecular sub-grouping of DLBCL patients. First, the prognostic information could inform the choices and expectations of patients and their physicians. Second, the important molecular differences in these subgroups form the basis of testing different targeted therapies in these patients. The possibility of a differential response to therapy among ABC and GCB DLBCLs is supported by data that suggest that the benefit of receiving a proteosome inhibitor, bortozemib, is predominantly limited to those patients who have ABC DLBCL. However, the clinical distinction of the subgroups of DLBCL using immunohistochemistry is difficult with current methods distinguishing GCB DLBCL from non-GCB DLBCL with limited success.
  • Mature B cell differentiation is important for the development of adaptive immunity. The process is also of interest because B cell malignancies are common and retain a number of features derived from their normal counterpart B cell subsets. Unlike other maturation pathways in the hematopoietic and other cell lineages, successive stages of mature B cells do not simply signify progressive differentiation away from the stem cell stage. Rather, each stage represents a specialized state with specific functions. Thus, germinal center (GC) cells interact with CD4 T cells and dendritic cells and undergo somatic hypermutation and Ig-heavy chain class-switching. On the other hand, plasma cells secrete immunoglobulin, while memory cells are primed to proliferate and differentiate into plasma cells upon repeat contact with antigen. The specialized functions demand a finely tuned program of gene regulation.
  • MicroRNAs represent a novel class of biomarkers that provide new opportunities for clinical translation. First, intact microRNAs can be isolated from tissues preserved using standard methods, such as formalin fixed, paraffin embedded (FFPE) tissue. Thus, microRNA-based biomarkers could be easy to translate to clinical use. Second, microRNAs can be readily assayed using real-time PCR and other methods available in conventional pathology.
  • SUMMARY
  • In an aspect the disclosure provides an isolated nucleic acid molecule having at least 80% sequence identity to any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof. Embodiments provide for sequence identity of at least 90% or 95%.
  • In an aspect the disclosure provides an isolated nucleic acid molecule comprises any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof. Embodiments provide for isolated nucleic acid molecules comprising a primary miRNA, a precursor miRNA, a mature miRNA, or a DNA molecule coding therefore. Embodiments further provide for a cDNA molecule comprising sequence that corresponds to a miRNA sequence of any one of SEQ ID NOs: 763-1350 or 1565.
  • Aspects of the disclosure provide compositions, pharmaceutical compositions, vectors, host cells, and DNA libraries comprising at least one nucleic acid molecule described herein.
  • In an aspect the disclosure provides a method of determining the B cell stage of a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 4.
  • In an aspect the disclosure provides a method of identifying a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 4.
  • In an aspect the disclosure provides a method of diagnosing a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 4.
  • In an aspect the disclosure provides a method of identifying a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in any one of Tables 7 to 35.
  • In an aspect the disclosure provides a method of diagnosing a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in any one of Tables 7 to 35.
  • Embodiments of these aspects provide for identification or diagnosis of a B cell malignancy selected from chronic lymphocytic leukemia, follicular lymphoma, Hodgkin's lymphoma, activated B-cell diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL, and Burkitt lymphoma.
  • In an aspect the disclosure provides a method of determining whether a B cell malignancy in a sample is Burkitt lymphoma, activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 10, column “BL miRNA list”; Table 14, column “BL High”; Table 11; Table 14, column “ABC High”; Table 10, column “GCB miRNA list”; Table 14, column “GCB High”; Table 32, or Table 35.
  • In an aspect the disclosure provides a method of determining whether a B cell malignancy in a sample is Burkitt lymphoma, activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in at least one column labeled “GCBvsBL” or “GCBvsABC” in Table 7 or “ABCvsBL” in Table 8.
  • In an aspect the disclosure provides a method of determining whether a B cell malignancy in a sample is activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 35.
  • In an aspect the disclosure provides a microarray comprising miRNA-specific probe oligonucleotides wherein at least one miRNA-specific probe oligonucleotide is specific for a sequence of SEQ ID NOs: 763-1350 or 1565, or any combination thereof.
  • In an aspect the disclosure provides a kit comprising at least one primer sequence that can detect any one of SEQ ID NOs: 763-1350 or 1565, or a combination thereof.
  • In an aspect the disclosure provides a kit comprising at least one isolated nucleic acid molecule having a sequence of any one of SEQ ID NOs: 1351-1564.
  • In an aspect, the disclosure provides a method of identifying a B cell malignancy comprising determining the level of expression of at least one microRNA selected from the microRNAs listed in Table 4. In certain embodiments, a method comprises determining the level of expression of at least one microRNA selected from the microRNAs listed in Tables 7-35.
  • Other aspects and embodiments will be apparent to one of skill in the art in light of the following detailed description.
  • DESCRIPTION OF THE FIGURES
  • FIG. 1 shows that mature B cell subsets demonstrate distinct microRNA profiles. FIG. 1A is a diagram showing the overall schema of mature B cell differentiation. FIG. 1B shows selection of B cell subsets using flow cytometry. FIG. 1C shows the distinction between naive and memory B cells based on IgD and CD27 expression using flow cytometry. FIG. 1D shows relative expression of microRNA in the naive to germinal center B cell transition. FIG. 1E shows relative expression of mRNA in the naive to germinal center B cell transition. FIG. 1F shows relative expression of microRNA in the germinal center B cell to plasma cell transition. FIG. 1G shows relative expression of mRNA in the germinal center B cell to plasma cell transition. FIG. 1H shows relative expression of microRNA in the germinal center B cell to memory B cell transition. FIG. 1I shows relative expression of mRNA in the germinal center B cell to memory B cell transition. In FIGS. 1D, 1F, and 1H, miRNAs that were, on average, at least 2-fold differentially expressed at a false discovery rate of less than 5% are shown according to the color scale. In Figures and 1E, 1G, and 1I, mRNAs that were, on average, at least 2-fold differentially expressed at a false discovery rate of less than 1% are shown according to the color scale. FIG. 1J shows that expression of certain microRNA processing genes, DGCR8, DICER1, EIF2C2, DROSHA, and XP05 is unchanged among the B cell subsets (P>0.1 in all cases).
  • FIG. 2 shows experimental validation of the interaction of miR-223, which is expressed highly in naive and memory B cells compared to germinal center B cells, and targets the transcription factor LM02. FIG. 2A shows base-pairing of the 3′UTR of the LM02 gene with nucleotides 1-8 of miR-223. This 8-mer is highly conserved across a number of species and serves as a potential binding site for miR-223. FIG. 2B shows the effects of over-expression of miR-223 in germinal center lymphoma-derived BJAB cells in 3 separate experiments. FIG. 2C shows the relative LM02 protein expression from a representative experiment (from 3 replicates) transfecting a scrambled control versus a precursor for miR-223 in BJAB cells. FIG. 2D shows average expression of LM02 relative to Actin over three Western blots of BJAB cells transfected with a scrambled control versus a precursor for miR-223. FIG. 2E shows luciferase activity in BJAB cells transfected with a vector comprising either a luciferase gene coupled to the 3 ′UTR of the LM02 gene or a luciferase gene coupled to the 3 ′UTR of the LM02 gene with the miR-223 binding site mutated, and cotransfected with miR-223.
  • FIG. 3 shows experimental validation of the interaction of miR-9 and miR-30, which are expressed highly in germinal center B cells compared to plasma cells and target the transcription factor PRDM1. FIG. 3A shows base-pairing of the 3′UTR of the PRDM1 gene with the 5′ seed region of miR-9 and the miR-30 family. FIG. 3B shows the effects of over-expressing miR-9 and 2 members of the miR-30 family, miR-30b and miR-30d, in plasma cell myeloma-derived U266 cells in 3 separate experiments. FIG. 3C shows the relative PRDM1 protein expression from a representative experiment (from 3 replicates) transfecting a scrambled control versus a precursor for miR-9, miR-30b, or miR-30d in U266 cells. FIG. 3D shows the average expression of PRDM1 relative to Actin over three Western blots of U266 cells transfected with a scrambled control versus a precursor for miR-9, miR-30b, or miR-30d. (P<0.05 for miR-30b and miR-30d, P=0.08 for miR-9.) FIG. 3E shows repression of luciferase activity from the PRDM1 3′UTR construct by overexpression of miR-9, miR-30b, and miR-30d wild-type and mutant sequences.
  • FIG. 4 shows that expression of microRNAs in normal B cells is conserved in certain B cell malignancies. FIG. 4A shows lineage prediction of both IgV mutated and unmutated chronic lymphocytic leukemia, germinal center B cell derived DLBCL, and Burkitt lymphoma based on differential expression of microRNAs in normal naïve B cells and germinal center B cells (microRNAs depicted in FIG. 1D). FIG. 4B shows miRNAs that were found to be differentially expressed (P<0.05) in malignant cells and normal cells as discussed in Example 5. FIG. 4C shows cloning frequency of miRNAs in unselected mature B cells (N=3) and certain B cell malignancies (N=42) from a previously published study (“sequencing data”), as discussed in Example 5. FIG. 4D shows differentially expressed miRNAs that distinguish Burkitt lymphoma, activated B cell-like (ABC) diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL (GCB DLBCL), and chronic lymphocytic leukemia. Predictor miRNAs from each pair-wise comparison that distinguish each entity are shown in the boxes.
  • FIG. 5 shows the distribution of miRNAs present in B-cell subsets.
  • FIG. 6 shows that certain microRNA targets are expressed at lower levels. FIG. 6A shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in germinal center B cells compared to naive cells. FIG. 6B shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in germinal center B cells compared to plasma cells. FIG. 6C shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in the germinal center B cells compared to memory B cells.
  • FIG. 7 shows that differentially expressed transcription factors are frequently microRNA targets. In FIG. 7A, the left panel indicates the proportion of transcription factors that are differentially expressed in the naive to germinal center B-cell transition that are also predicted targets of differentially expressed miRNAs. The right panel indicates the proportion of transcription factors that are not differentially expressed and also are predicted targets of differentially expressed miRNA in that stage-transition. The p-value indicates the results of a chi-squared test for the enrichment of predicted miRNA targets among the differentially expressed transcription factors. FIG. 7B shows a similar analysis of the germinal center to plasma cell transition. FIG. 7C shows a similar analysis of the germinal center to memory cell transition.
  • FIG. 8 shows that Mybl transcript levels decrease with miR-223 overexpression. FIG. 8A shows base-pairing of the 3′UTR of the MYBL1 gene with nucleotides 2-8 of miR-223. This 7-mer is highly conserved across a number of species and serves as a potential binding site for miR-223. FIG. 8B shows the effects of over-expression of miR-223 in germinal center lymphoma-derived BJAB cells in 3 separate experiments.
  • FIG. 9 shows the specificity of real-time PCR probes for members of the miR-30 family.
  • FIG. 10 shows the results of leave one out cross validation applied to the predictors for Burkitt lymphoma, chronic lymphocytic leukemia, activated B-cell diffuse large B-cell lymphoma, and germinal center B-cell DLBCL.
  • FIG. 11 shows differentially expressed miRNAs that distinguish activated B cell-like diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL (GCB DLBCL), Burkitt lymphoma, chronic lymphocytic leukemia, follicular lymphoma, and Hodgkin's lymphoma. Predictor miRNAs from each pair-wise comparison that distinguish each entity are shown in the boxes.
  • DETAILED DESCRIPTION
  • All patent and non-patent literature references that are cited herein are incorporated herein by reference in their entirety.
  • In a general sense, the disclosure relates to nucleic acid sequences, such as microRNAs (miRNA), as well as to the identification and analysis of microRNA expression levels and/or patterns in B cells. Through concomitant microRNA and mRNA profiling, the inventors have identified regulatory roles for microRNAs at each stage in mature B cell differentiation. This provides methods identifying microRNA-mediated regulation of oncogenes and key transcription factors in B cell differentiation. This work establishes the landscape of normal microRNA expression in mature B cells and its role in regulating normal B cell differentiation. Further, our work demonstrates that in contrast to the described down-regulation in other malignancies, stage-specific microRNAs are retained in B cell malignancies. The lineage of common B cell malignancies can be predicted based upon miRNA profiles of normal B cells, pointing to a role for microRNAs in the maintenance of mature B cell phenotypes in normal and malignant B cells.
  • In an aspect, the disclosure relates to an isolated nucleic acid molecule comprising: (a) a nucleotide sequence as shown in Table 32; (b) a nucleotide sequence which is the complement of (a), (c) a nucleotide sequence comprising a sequence identity of at least 80%, (e.g., 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or at least 99%), to a sequence of (a) or (b) and/or (d) a nucleotide sequence which hybridizes under stringent conditions to a sequence of (a), (b) and/or (c). In some embodiments, the identity of sequence (c) to a sequence of (a) or (b) is at least 90%. In other embodiments, the identity of sequence (c) to a sequence of (a) or (b) at least 95%. The percent identity can be calculated by any routine method used by one of skill in the art such as, for example, the methods described herein.
  • In embodiments, the isolated nucleic acid molecule relates to a miRNA molecule and analogs thereof, a miRNA precursor molecule, or a primary miRNA molecule, as well as to DNA molecules encoding miRNA, miRNA precursor, or primary miRNA molecules. Accordingly, in such embodiments, the isolated nucleic acid molecule can function as a miRNA molecule under suitable conditions. Suitable conditions include, but are not limited to, various buffer systems that approximate physiologically relevant ionic concentrations and pHs, as well as physiological conditions.
  • In some embodiments, the nucleic acid molecule comprises a sequence that hybridizes to a nucleotide sequence as shown in Table 32, a complementary sequence thereof or a nucleic acid molecule having at least 80% sequence identity under stringent hybridization conditions. The basic parameters affecting the choice of hybridization conditions and guidance for devising suitable conditions are set forth by Sambrook, et al. (See, 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; and Current Protocols in Molecular Biology, 1995, Ausubel et al., eds., John Wiley & Sons, Inc.), and can be readily determined by those of ordinary skill in the art based on, for example, the length and/or base composition of the DNA. Generally, stringent salt concentration will ordinarily be less than about 750 mM NaCl and 75 mM trisodium citrate, or less than about 500 mM NaCl and 50 mM trisodium citrate, or even less than about 250 mM NaCl and 25 mM trisodium citrate. High stringency hybridization conditions can be obtained by adding an amount of organic solvent (e.g., at least about 35% to about 50% formamide). Stringent temperature conditions will ordinarily include temperatures of at least about 30° C., (e.g., at least about 37° C., 42° C., 45° C., 50° C., or 55° C.). Varying additional parameters, such as hybridization time, the concentration of detergent (e.g., 0.1-1.0% sodium dodecyl sulfate (SDS)), and the inclusion or exclusion of carrier DNA (e.g., about 100-200 μg/ml denatured salmon sperm DNA (ssDNA)), are well known to those skilled in the art. Stringent hybridization conditions are known in the art and include non-limiting examples such as, washing for 1 hr in 300 mM NaCl, 30 mM trisodium citrate and 0.1% SDS at 45-50° C.; washing for 1 h in 300 mM NaCl, 30 mM trisodium citrate and 0.1% SDS at 45-50° C.; in 500 mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 μg/ml denatured salmon sperm DNA (ssDNA) at 37° C.; or in 250 mM NaCl, 25 mM trisodium citrate, 1% SDS, 50% formamide, and 200 μg/ml ssDNA at 42° C. Useful variations on these conditions will be readily apparent to those skilled in the art.
  • The isolated nucleic acid molecules provided herein suitably have a length of from about 18 to about 100 nucleotides. In embodiments wherein the isolated nucleic acid molecules are miRNAs, the lengths of the miRNAs are suitably in an expected range for the particular type of miRNA molecule. For example, mature miRNAs are typically from about 15 to about 28 nucleotides in length, and suitably have a length of about 19 to about 24 nucleotides (e.g., 19, 20, 21, 22, 23, or 24 nucleotides). Precursor miRNAs typically comprise the mature miRNA sequence and contain a stem-loop structure, suitably of length of about 50 to about 90 nucleotides (e.g., 50, 55, 60, 65, 70, 75, 80, 85, or 90 nucleotides). Primary miRNAs (e.g., a primary transcript comprising a precursor miRNA) can suitably have a length of greater than 100 nucleotides.
  • The nucleic acid molecules can be provided in either a single-stranded or double-stranded form. Typically, a miRNA as such is identified as a single-stranded molecule, while the precursor miRNA is typically at least partially self-complementary and capable of forming double-stranded portions, e.g. stem- and loop-structures. DNA molecules encoding the miRNA and miRNA precursor molecules (e.g., expression vectors, cloning vectors, and the like) are typically double-stranded. The individual nucleic acids that comprise the isolated nucleic acid molecules can be selected from RNA, DNA, or nucleic acid analog molecules, such as chemically modified sugar (e.g., 2′-modified (2′-F, 2′-OMe, etc.) or backbone (e.g., phosphorothioates), or cap (e.g., 5′- and/or 3′-abasic groups) moieties of ribonucleotides or deoxyribonucleotides. Other nucleic acid analogs, such as peptide nucleic acids (PNA) or locked nucleic acids (LNA), are also suitable in various embodiments described herein. In some embodiments the nucleic acid molecules can comprise any combination of nucleic acid analog(s).
  • While many of the nucleic acid molecules in the Tables are identified as RNA sequences, e.g., miRNAs, the disclosure of those sequences should be understood to encompass the corresponding DNA (e.g., cDNA) sequences, wherein the uracil (U) nucleotides of the disclosed RNAs are substituted by thymidine (T) nucleotides in the corresponding DNA. One of skill in the art is able to generate such DNA sequences (e.g., cDNA) through routine microbiological techniques known in the art such as, for example, reverse transcription using methods that incorporate the reverse transcriptase enzyme.
  • In another aspect, the disclosure provides a recombinant expression vector comprising a recombinant nucleic acid sequence operatively linked to an expression control sequence, wherein expression of the recombinant nucleic acid sequence provides a miRNA sequence, a precursor miRNA sequence, or a primary miRNA sequence as described herein. The resulting sequence (e.g., primary or precursor miRNAs) can optionally be further processed to provide the miRNA sequence. In embodiments, the recombinant expression vector comprises at least one sequence in Table 32. Any suitable expression vector can be used such as, for example, a DNA vector (e.g., viral vector, plasmid, etc.). In some embodiments the expression vector is selected for expression in a eukaryotic cell such as, for example, a mammalian cell. One of skill in the art will be able to select an appropriate vector based on the particular application and/or expression system to be employed.
  • Thus, embodiments provide nucleic acid constructs in the form of plasmids, vectors, transcription or expression cassettes which comprise at least one nucleotide sequence encoding a miRNA described herein, or fragments thereof, and a suitable promoter region. Suitable vectors can be chosen or constructed, which contain appropriate regulatory sequences, such as promoter sequences, terminator sequences, polyadenylation sequences, enhancer sequences, marker genes and other sequences as desired. Vectors can be plasmids, phage (e.g. phage, or phagemid) or viral (e.g. lentivirus, adenovirus, AAV) or any other appropriate vector. For further details see, for example, Molecular Cloning: a Laboratory Manual: 2nd edition, Sambrook et al., 1989, Cold Spring Harbor Laboratory Press.
  • Relatedness of Nucleic Acid Molecules/Sequences
  • The term “identity” refers to a relationship between the sequences of two or more two or more nucleic acid molecules, as determined by comparing the sequences. In the art, “identity” also means the degree of sequence relatedness between amino acid or nucleic acid molecule sequences, as the case may be, as determined by the match between strings of nucleotide or amino acid sequences. “Identity” measures the percent of identical matches between two or more sequences with gap alignments addressed by a particular mathematical model or computer programs (i.e., “algorithms”).
  • Identity of related nucleic acid molecules can be readily calculated by known methods, including but not limited to those described in Computational Molecular Biology, Lesk, A. M., ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, D. W., ed., Academic Press, New York, 19933; Computer Analysis of Sequence Data, Part 1, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M. Stockton Press, New York, 1991; and Carillo, H., and Lipman, D., SIAM J. Applied Math., 48:1073 (1988).
  • Non-limiting methods for determining identity are designed to give the largest match between the sequences tested. Methods to determine identity are codified in publicly available computer programs. Preferred computer program methods to determine identity between two sequences include, but are not limited to, the GCG program package, including GAP (Devereux, et al., Nucleic Acids Research 12:387 [1984]; Genetics Computer Group, University of Wisconsin, Madison, Wis.), BLASTN, and FASTA (Atschul et al., J. Molec. Biol. 215:403-410 [1990]). The BLAST X program is publicly available from the National Center for Biotechnology Information (NCBI) and other sources (BLAST Manual, Altschul] et al., NCB NLM NIH Bethesda, Md. 20894; Altschul et al., J. Mol. Biol. 215:403-410 [1990]). The well known Smith Waterman algorithm may also be used to determine identity.
  • Exemplary parameters for nucleic acid molecule sequence comparison include the following:
  • Algorithm: Needleman and Wunsch, J. Mol Biol. 48:443-453 (1970)
  • Comparison matrix: matches=+10, mismatch=0
  • Gap Penalty: 50
  • Gap Length Penalty: 3
  • The GAP program is also useful with the above parameters. The aforementioned parameters are the default parameters for nucleic acid molecule comparisons.
  • Other exemplary algorithms, gap opening penalties, gap extension penalties, comparison matrices, thresholds of similarity, etc. can be used by those of skill in the art, including those set forth in the Program Manual, Wisconsin Package, Version 9, September 1997. The particular choices to be made will depend on the specific comparison to be made, such as DNA to DNA or RNA to DNA; and additionally, whether the comparison is between given pairs of sequences (in which case GAP or BestFit are generally preferred) or between one sequence and a large database of sequences (in which case FASTA or BLASTA are preferred).
  • In an aspect, the disclosure provides a vector comprising the isolated polynucleotide as described herein such as, for example one or more of SEQ ID NOs 773-1046 or 1450-1542. In embodiments, the vector can be any type of vector that finds use as a vehicle to transfer foreign genetic material into a cell. Non-limiting examples of vectors include plasmids, viral vectors (e.g., derived from lentivirus, adenovirus, adeno-associated virus (AAV), retrovirus, etc.), bacteriophage, cosmids, and artificial chromosomes. In embodiments, the vector can be an expression (or expression constructs) for driving expression of the polynucleotide in a target cell. Vectors and methods for inserting them into a target cell are known in the art [See, e.g., Sambrook et al., 1989].
  • In an aspect, the disclosure provides recombinant cells that comprise the vectors and/or polynucleotides described herein. The cells can be any cell suitable as a host for recombinant nucleic acid molecules, and selected based on well known techniques. Techniques for generating and maintaining recombinant cells are known in the art, such as those described in Sambrook et al., 1989.
  • The term “B cell malignancy,” as used herein, refers to a malignancy derived from any stage of B cell, including, but not limited to, naïve cells, germinal center cells, memory B cells, and plasma cells. Examples of B cell malignancies include, but are not limited to, mantle cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, germinal center B-cell like diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, and activated B-cell like DLBCL.
  • In an aspect, the disclosure provides a method of distinguishing B cell malignancies on the basis of the B-cell origin. In certain embodiments, methods of diagnosing B cell malignancies on the basis of the B-cell origin are provided. In certain such embodiments, a B cell malignancy is determined to be derived from a particular B-cell stage. The B-cell origin of a B cell malignancy may be determined, in certain embodiments, by detecting one or more microRNAs that can be used to distinguish B-cell stages. Certain exemplary B-cell stages include, but are not limited to, naïve cells, germinal center cells, memory B cells, and plasma cells. Certain exemplary microRNAs that can be used to distinguish B-cell stages are shown in Table 4. In various embodiments, the method comprises detecting at least one, at least two, at least five, at least 10, at least 20, at least 30, at least 50, at least 75, or at least 100 microRNAs.
  • In certain embodiments, a panel of microRNAs is selected that will allow determination of the B cell stage from which a B cell malignancy is derived. For example, in certain embodiments, two or more microRNAs from Table 4 are selected such that detection of the levels of those microRNAs in a B cell malignancy will indicate whether the B cell malignancy is derived from naïve, germinal center, plasma, or memory B cells. In various embodiments, the panel of microRNAs comprises at least one, at least two, at least five, at least 10, at least 20, at least 30, at least 50, at least 75, or at least 100 microRNAs from Table 4. One skilled in the art can select a suitable panel of microRNAs, including one or more microRNAs from Table 4, according to the intended use of the panel.
  • As described throughout the disclosure, the methods herein can include detecting one or a plurality of miRNAs. When the term “at least” is used in association with a number (e.g., “at least 20”) that term will be understood to include 20 as well as optionally any integer after 20 and up to and including the total number of microRNAs disclosed herein.
  • In some embodiments, a B cell malignancy derived from naïve cells is mantle cell lymphoma. In other embodiments, a B cell malignancy derived from germinal center cells includes, but is not limited to, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, or germinal center B-cell like diffuse large B cell lymphoma (DLBCL). In other embodiments, a B cell malignancy derived from memory B cells includes, but is not limited to, chronic lymphocytic leukemia or small lymphocytic lymphoma. In some embodiments, a B cell malignancy derived from plasma cells includes, but is not limited to, multiple myeloma or activated B-cell DLBCL.
  • Certain B cell malignancies can be difficult to distinguish using current methodologies. In extreme cases, almost any B cell malignancy can be confused with another. As illustrative examples, Burkitt lymphoma and DLBCLs are often confused. Similarly, mantle cell lymphoma and small lymphocytic lymphoma can also be confused. Burkitt lymphoma and germinal center DLBCL are both derived from germinal center cells, while activated B-cell DLBCL is derived from plasma cells. Thus, if a B cell malignancy appears to be Burkitt lymphoma or a DLBCL, in certain embodiments, microRNA analysis can be used to narrow down the B cell malignancy to either a germinal center cell-derived B cell malignancy or a plasma cell-derived B cell malignancy. If the B cell malignancy is plasma-cell derived, then it may be activated B-cell DLBCL.
  • Thus, in certain embodiments, when the identity of a particular B cell malignancy has been narrowed down to two or more possible B cell malignancies, and at least two of those B cell malignancies are derived from different B cell stages, microRNAs that distinguish certain B cell stages can be used to further narrow down the identity of the B cell malignancy. In certain embodiments, microRNAs that distinguish certain B cell stages can be used to identify the B cell malignancy. One or more such microRNAs can be selected, in certain embodiments, from the microRNAs in Table 4. One skilled in the art can select a suitable set of microRNAs, including at least one microRNA from Table 4, for distinguishing particular B cell stages.
  • In an aspect, the disclosure provides a method of identifying a B cell malignancy comprising detecting one or a plurality of microRNAs. In certain embodiments, the method can provide a diagnosis of a B cell malignancy. In certain embodiments, one or more microRNAs that are characteristic of a particular B cell malignancy are used to identify the B cell malignancy. In certain embodiments, the identity of the B cell malignancy is first narrowed down to a list of two or more particular B cell malignancies using, for example, tumor morphology and/or immunohistochemistry and/or microRNA detection, e.g., to determine the B cell stage from which the tumor is derived. Certain exemplary microRNAs that can be used to identify B cell malignancies are shown in the Tables (e.g., Tables 7-35).
  • In certain embodiments, methods of identifying B cell malignancies comprise detecting one or more microRNAs from one or more of Tables 7 to 15, and Appendix B, Tables 16 to 30. That is, in certain embodiments, a panel of microRNAs is selected that will identify a B cell malignancy as being one of a particular selection of B cell malignancies. As a non-limiting example, a panel of microRNAs can be designed to identify a B cell malignancy as one of Burkitt lymphoma, ABC DLBCL, or GCB DLBCL. In certain such embodiments, the panel of microRNAs comprises at least one microRNA from Table 10, column “BL miRNA list” and/or Table 14, column “BL High”; at least one microRNA from Table 11 and/or Table 14, column “ABC High”; and at least one microRNA from Table 10, column “GCB miRNA list” and/or Table 14, column “GCB High”.
  • When other methods indicate a particular identity for a B cell malignancy, in certain embodiments, microRNAs can be used to confirm that identification. Thus, for example, if a B cell malignancy is believed to be a Burkitt lymphoma, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 10, column “BL miRNA list” and/or Table 14, column “BL High”. Similarly, if a B cell malignancy is believed to be ABC DLBCL, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 11 and/or Table 14, column “ABC High”. If a B cell malignancy is believed to be GCB DLBCL, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 10, column “GCB miRNA list” and/or Table 14, column “GCB High”. If a B cell malignancy is believed to be chronic lymphocytic leukemia, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 12 and/or Table 15, column “CLL High”. If a B cell malignancy is believed to be Hodgkin's lymphoma, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 13 and/or Table 15, column “HL High”. If a B cell malignancy is believed to be follicular lymphoma, that identification can be confirmed by determining the expression level of one or more microRNAs listed in Table 10, column “FL miRNA list” and/or Table 15, column “FL High”.
  • In certain embodiments, when the identity of a B cell malignancy has been narrowed down to two B cell malignancies selected from Burkitt lymphoma, GCB DLBCL, ABC DLBCL, chronic lymphocytic leukemia, follicular lymphoma, and Hodgkin's lymphoma, the identity of the B cell malignancy can be determined by detecting one or more microRNAs from Tables 16 to 30.
  • As discussed in the Examples, the miRNAs described herein as differentially expressed in a B cell malignancy have been identified with high confidence, and thus, identification of one miRNA is adequate to perform the methods of identification and diagnosis disclosed herein. Accordingly, in various embodiments, the methods can comprise detecting at least one, at least two, at least five, at least 10, at least 20, at least 30, or at least 50 microRNAs in order to narrow down the identity of, or identify, a B cell malignancy.
  • As noted above, the treatment regimens and prognoses for the various B cell malignancies can differ significantly. Thus, determining the correct identity and/or origin of a B cell malignancy can be important for selecting an effective therapy and/or setting appropriate patient expectations.
  • B cell malignancy samples may be obtained and prepared using methods known in the art. One skilled in the art can select an appropriate method of obtaining a B cell malignancy sample according to various parameters, such as the age, size, medical history, and/or identity of the patient. One skilled in the art can select an appropriate method of preparing a B cell malignancy sample for analysis according to the B cell malignancy sample source, size, quality, and/or intended use. For example, in certain embodiments, a B cell malignancy sample is prepared in a manner that preserves microRNAs in the sample as much as practicable under the circumstances.
  • MicroRNAs can be detected using any method known in the art. Exemplary methods of detecting microRNAs include, but are not limited to, hybridization-based methods and amplification-based methods. Certain exemplary detection methods include, but are not limited to, arrays (including microarrays and bead-based arrays), in situ hybridization, Northern blotting, TaqMan probes, RT-PCR, real-time PCR, and direct sequencing. One skilled in the art can select a suitable detection method according to the sample source, size, quality, and/or particular application.
  • In certain embodiments, real-time PCR is employed to determine the expression level of a microRNA. In some embodiments a miRNA is considered present in a subpopulation if the cycling time (CT) is less than 36 in all three biological replicates, and a CT greater than 36 is undetected.
  • In certain embodiments, the expression level of a microRNA in a sample is determined relative to a control sample. A control sample may be selected, in various embodiments, because it is expected to have either high or low expression of the microRNA.
  • In certain embodiments, the expression level of a microRNA may be normalized to the expression level of a polynucleotide that is expected to be expressed at similar levels in several different cell types and/or at constant levels in the cell type being analyzed.
  • In certain embodiments, an identified miRNA from Tables 7-35 is used to distinguish one of the six exemplified B cell malignancies from the other malignancies. A “high” and a “low” in Tables 10 to 13 refer to at least a 2-fold difference in the expression of the identified miRNA when one lymphoma is compared to other lymphomas and benign lymph nodes.
  • In embodiments, mRNA levels can be profiled by using a microarray. In some embodiments, array elements with median signal intensities of less than 7 log 2 units across samples are removed from analysis. In embodiments, a gene is considered for further analysis if it is on-average 2-fold or higher differentially expressed in a binary comparison of B cell subsets and expressed in at least one of the two B cell subsets being compared.
  • In an embodiment, the level of at least one miRNA is measured by reverse transcribing RNA from a test sample obtained from a subject to provide a set of target oligodeoxynucleotides, hybridizing the target oligodeoxynucleotides to one or more miRNA-specific probe oligonucleotides (e.g., a microarray that comprises miRNA-specific probe oligonucleotides) to provide a hybridization profile for the test sample, and comparing the test sample hybridization profile to a hybridization profile generated from a control sample. An alteration in the signal of at least one miRNA in the test sample relative to the control sample is indicative of the subject either having, or being at risk for developing, a B-cell malignancy. In an embodiment, the signal of at least one miRNA is upregulated, relative to the signal generated from the control sample. In another embodiment, the signal of at least one miRNA is down-regulated, relative to the signal generated from the control sample. In some embodiments, the microarray comprises miRNA-specific probe oligonucleotides for a substantial portion of all known human miRNAs. In a further embodiment, the microarray comprises miRNA-specific probe oligonucleotides for one or more miRNAs selected from the group consisting of SEQ ID NOs: 763-1350, or 1565 and any combination thereof.
  • The microarray can be prepared from gene-specific oligonucleotide probes generated from known miRNA sequences. The array may contain two different oligonucleotide probes for each miRNA, one containing the active, mature sequence and the other being specific for the precursor of the miRNA. The array may also contain controls, such as one or more mouse sequences differing from human orthologs by only a few bases, which can serve as controls for hybridization stringency conditions. tRNAs and other RNAs (e.g., rRNAs, mRNAs) from both species may also be printed on the microchip, providing an internal, relatively stable, positive control for specific hybridization. One or more appropriate controls for non-specific hybridization may also be included on the microchip. For this purpose, sequences are selected based upon the absence of any homology with any known miRNAs.
  • The microarray may be fabricated using techniques known in the art. For example, probe oligonucleotides of an appropriate length, e.g., 40 nucleotides, are 5′-amine modified at position C6 and printed using commercially available microarray systems. Labeled cDNA corresponding to the target RNA sequence(s) is prepared by reverse transcribing the target RNA with labeled primer. Following first strand synthesis, the RNA/DNA hybrids are denatured to degrade the RNA templates. The labeled target cDNAs thus prepared are then hybridized to the microarray chip under typical hybridizing conditions. At positions on the array where the immobilized probe DNA recognizes a complementary target cDNA in the sample, hybridization occurs. The labeled target cDNA marks the exact position on the array where binding occurs, allowing automatic detection and quantification. The output consists of a list of hybridization events, indicating the relative abundance of specific cDNA sequences, and therefore the relative abundance of the corresponding complementary miRNAs, in the patient sample.
  • In an aspect, the disclosure relates to kits. Such kits can be used in methods of identifying a miRNA or mRNA described herein; an expression level or expression pattern of one or more miRNA(s) or mRNA(s) described herein; and/or identifying a B-cell malignancy. In some embodiments the kit can provide a diagnosis of a B-cell type and or a B-cell malignancy. In some embodiments the kit can differentiate one B-cell malignancy from other B-cell malignancies (e.g., ABC-DLBCL from GBC-DLBCL), and can provide information useful to a medical professional regarding a preferred course of therapeutic treatment. Suitably, a kit can comprise an isolated nucleic acid molecule or a plurality of isolated nucleic acid molecules as described herein (e.g., a sequence complementary to any of the miRNAs disclosed in the Tables). In embodiments, the isolated nucleic acid molecule can comprise a sequence of one or more RT-PCR target sequences, primers directed thereto, or a sequence complementary thereto. The kit can also include adapter nucleic acid molecules (e.g., universal adapter molecules for attachment to expressed miRNAs/mRNAs for reverse transcription and amplification); appropriate buffer systems and reagents, detectable labels, an energy source (e.g., ATP), and other agents and components that can be used in performing analysis of miRNA expression (e.g., in RT-PCR, deep sequencing, or microarray-based methods). Kits also include instructions for use.
  • It will be understood that any numerical value recited herein includes all values from the lower value to the upper value. For example, if a concentration range is stated as 1% to 50%, it is intended that values such as 2% to 40%, 10% to 30%, or 1% to 3%, etc., are expressly enumerated in this specification. These are only examples of what is specifically intended, and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application.
  • In an aspect, the disclosure provides a DNA library comprising one or more miRNA sequences from Tables 4-5, or 6-33. In a related aspect, the disclosure provides a method for generating such a DNA library. In an embodiment the library comprises a cDNA library that includes sequences derived from a sample of the miRNAs or, in addition or alternatively, the mRNA purified from a particular source such as, for example, a collection of cells, a particular tissue, or an entire organism. In embodiments, the source of the cDNA library is a B cell, such as a B cell in any stage (e.g., naïve, germinal center, memory, activated, or plasma, etc.) or a B cell malignancy (e.g., mantle cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, Burkitt lymphoma, germinal center B-cell like diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, and activated B-cell like DLBCL). Typically, the isolated miRNA (or mRNA) is converted to a DNA template by reverse transcription, and comprises the cDNA version of the expressed RNA (e.g., miRNA or mRNA). Thus, a library can represent the cDNA version of the active “transcriptome” in a particular source under the physiological, developmental, or environmental conditions that existed when the miRNA/mRNA was purified.
  • In an embodiment, the library comprises a miRNA sequence described in Tables 4-5; 7-33. In embodiments, the library comprises at least one of SEQ ID NOs 763-1350 or 1565, and any combination thereof. In an embodiment, the library comprises a collection of miRNA sequences comprising SEQ ID NOs 763-1350 or 1565. In embodiments the library can be used to identify and/or differentiate a B-cell malignancy from other B-cell malignancies. In such embodiments, the library comprises at least one miRNA sequence selected from those listed in any of Tables 4 or 7-35.
  • As used herein, a “library” is a collection of DNA sequences that is stored and propagated in a population of microorganisms through standard molecular cloning processes. A DNA library can be of any type such as, for example, a cDNA library (formed from reverse-transcribed RNA) or a genomic library (formed from genomic DNA). The DNA library can be used in any routine application or technique known in the art (e.g., gene discovery; cloning of full-length cDNAs to identify/study gene function; miRNA/mRNA expression in different cells or tissues; splice variants in different cells or tissues) and, in some embodiments, can depend on the source of the original DNA fragments. In embodiments, the library can be used to isolate, characterize, and/or quantify the actively expressed miRNA is a population of cells such as, for example, B-cells or B-cell malignancies. In some embodiments, the library can be used to study miRNA-protein interactions or miRNA-based regulation of protein expression or activity.
  • Any known method of library preparation can be used to make the library described herein, including the methods described in the detailed description and non-limiting Examples. Further general techniques can be based on the methods and techniques known in the art, (see, e.g., RNA Methodologies: A Laboratory Guide for Isolation and Characterization (R. E. Farrell, Academic Press, 1998); cDNA Library Protocols (Cowell & Austin, eds., Humana Press; Functional Genomics (Hunt & Livesey, eds., 2000); and the Annual Review of Genomics and Human Genetics (E. Lander, ed., yearly publications by Annual Reviews). Suitably, the nucleotide sequences of interest in a library are preserved as inserts in a plasmid or the genome of a bacteriophage that has been used to infect bacterial cells. There are differences in the cloning vectors and techniques used in library preparation, but in general each DNA fragment is uniquely inserted into a cloning vector and the pool of recombinant DNA molecules is then transferred into a population of bacteria or yeast such that each organism contains on average one construct (vector+insert). The DNA molecules are copied and propagated along with the population of organisms in culture (thus, effectively, “cloned”). Accordingly, in some embodiments, the term “library” can refer to a population of organisms, each of which carries a DNA molecule inserted into a cloning vector, or alternatively to the collection of all of the cloned vector molecules.
  • An “increased level” of expression, as used herein, refers to a level of expression that is at least 2-fold greater than the level of expression in a control cell type or tissue. In various embodiments, the level of expression is at least 2.5-fold, at least 3-fold, at least 5-fold, or at least 10-fold, greater than the level of expression in a control cell. Exemplary control cells and tissues include, but are not limited to, normal cells, benign lymph nodes, and other B cell malignancies. In certain embodiments, benign lymph nodes are used as a control tissue. Such benign lymph node tissue contains a variety of cell types.
  • A “decreased level” of expression, as used herein, refers to a level of expression that is less than 50% of the level of expression in a control cell.
  • The term “differentially expressed” or “differential expression” relates to a difference in the observed or detected level of expression of a biomolecule such as, for example, nucleic acids (e.g., a polynucleotide, mRNA, miRNA, etc.) or amino acid sequence (e.g., protein, polypeptide, etc.) in a test sample relative to the observed or detected level of expression of the same biomolecule in a control sample or other reference (e.g., a previously established reference level). The difference in expression can be either an increase or a decrease in the expression of the biomolecule in the test sample relative to the control sample.
  • The Examples that follow provide further illustration of certain aspects and embodiments described in the foregoing description. These illustrative Examples should not be interpreted as limiting the scope of the appended claims.
  • EXAMPLES Example 1 Materials and Methods
  • Patient Sample Processing
  • B cell populations were obtained from young patients undergoing routine tonsillectomy using a protocol approved by the Clinical Center at the National Institutes of Health. Patient tonsils were disaggregated and separated by Ficoll. The mononuclear cell layer was harvested, washed in PBS, and resuspended in ACK lysing buffer to remove small numbers of red blood cells. After a wash and resuspension with 10 ml of PBS with 10% Bovine Serum Albumin, cells were counted and 200 million were stained with fluorochrome-tagged monoclonal antibodies to CDI9, IgD, CD38 and CD27. The specific monoclonal antibodies employed were anti-CDI9-PE-Cy5.5, anti-IgD-FITC, anti-CD27-PE, and anti-CD38-APC, all from BD Biosciences and BD Pharmingen (San Jose Calif.). Cells were sorted using the MoFlo Cell sorter (Dako Cytomation, Colorado Springs, Colo.) into naive B cells (CDI9+IgD+CD2TCD38+), germinal center B cells (CDI9+IgD−CD38++), memory B cells (CDI9+IgD−CD27+CD38dim) and plasma cells (CDI9dimIgD−CD27++CD38+++). Three replicates of each B cell subset were obtained from separate patients. The sample purity was verified by FACS and found to be over 90% in all cases.
  • Tumor specimens were obtained from patients who were examined under a protocol approved by the Duke University Medical Center Institutional Review Board. The pathologic diagnosis of the samples was verified prior to analysis. Samples from patients with diffuse large B cell lymphoma were further subclassified as described previously. See Hans et al. (2004) Blood 103: 275-282. Chronic lymphocytic leukemia samples were processed and purified as described previously. See Volkheimer et al. (2007) Blood 109: 1559-1567. Total RNA was extracted using the phenol-chloroform method to preserve miRNAs, using Ambion reagents.
  • microRNA Profiling Using Multiplexed Real-Time PCR
  • MiRNA expression profiling was conducted using the Applied Biosystems 384-well multiplexed real-time PCR assay using 400 ng of total RNA. Eight reactions, each containing 50 ng of RNA and a multiplex looped primer pool with endogenous small nucleolar (sno)-RNA controls, were used to reverse-transcribe the miRNAs in parallel fashion. Each completed reaction was loaded onto the 384-well plate per manufacturer's instructions, and real-time PCR was run on the ABI 7900HT Prism. For each 384-well plate, we used the automatically determined cycle-threshold (CT) using the SDS 2.2.1 software (Applied Biosystems). Consistent with manufacturer recommendations, we considered CT greater than 36 as undetected. A miRNA was considered to be present in a subpopulation if the CT was less than 36 in all three biological replicates. The probes deemed to be present were normalized to the average expression of a sno-RNA control. The expression values were calculated as 2−ΔCT, then median centered to 500 and log 2-transformed.
  • Gene Expression (mRNA) Profiling Using Microarrays
  • Gene expression profiling and normalization were performed using methods identical to those we have described previously. See Dave et al. (2004) N. Engl. J. Med. 351: 2159-2169. Array elements with median signal intensities of less than 7 log 2 units across the samples were removed from analysis, in order to exclude poorly measured genes and genes not appreciably expressed in the samples. Genes that were on-average 2-fold or higher differentially expressed in a binary comparison of B cell subsets, and appreciably expressed in at least one of the 2 B cell subsets being compared, were selected for further analysis as described below. The data have been deposited in the publicly available Gene Expression Omnibus database (GSE12366).
  • MiRNA Profiling Using Microarray
  • MiRNA expression profiling from human B cell malignancies was conducted using up to 1 μg of total RNA from sample and reference (normal lymph node), which were labeled with Cy3 or Cy5 fluorescent dyes, using the miRNA/LNA labeling kit (Exiqon, Denmark). The fluorescently labeled samples were combined and hybridized to a miRNA microarray (v.10.0, Exiqon, Denmark), in a nitrogen atmosphere. The micro array slides were scanned with GenePix 4100 Scanner. The quantified signals were normalized using the global Lowess algorithm, using Genespring (Agilent) software. The intensity values for multiple spots were averaged and the normalized values were log 2-transformed. Missing values were replaced with the lowest value for analysis.
  • MiRNA Target Prediction
  • Annotated genes on the U133plus 2.0 array were matched to the miRNA target list downloaded from TargetScan (www.targetscan.org). For the purpose of this study, a target gene was defined by the presence of a seed sequence match (nucleotides 2-8) and conservation of the seed sequence and 3 ′UTR in humans, dog, rat, mouse and chicken. Additional conservation was examined in miRNA target genes selected for experimental validation. The distribution of the mRNA expression for these genes was plotted as a density plot using the Splus statistical software (Insightful Corporation). The difference in distribution between the B cell subsets was calculated using a two-sample, 1-sided Kolmogorov-Smirnov test to examine the hypothesis that being a miRNA target conferred repression in the appropriate population (consistent with the known biology of miRNA effects).
  • The 3′UTRs of LM02, MYBL1 and PRDM1 were aligned using Blastz alignment of Human, Chimp, Mouse, Rat, Dog, Chicken, Frog (Xenopus) and Zebrafish, and were displayed using the UCSC genome browser. The conservation of miR-223 seed sequence and the 3′UTRs of LM02 and MYBL1, as well as that of the miR-30 family and miR-9 on PRDM1, were thus verified.
  • Western Blot
  • RIPA Lysis buffer (1× phosphate-buffered saline [PBS], 1 Nonidet P-40, 0.5% sodium deoxycholate, 0.1% SDS, 10 mM phenylmethylsulfonyl fluoride, 1 μg/mL aprotinin, and 100 mM sodium orthovanadate) was added to 750,000 cells and incubated on ice for 30 minutes. The mixture was spun down and the supernatant was transferred to a new tube as the whole cell extract. A total of 20 μg of cell lysate was separated on a 4-18% Tris-Bis NuPAGE gel (Invitrogen) and transferred using the iBlot transfer device (Invitrogen) program 3 for 7 minutes (LM02 detection) or program 2 for 6 minutes (PRDM1). The blots were probed using 1:200 mouse-anti-LM02 (Santa Cruz Biotechnologies SC-65736), 1:750 mouse-anti-Blimp-1 (Santa Cruz Biotechnologies SC-66015) or 1:5000 goat-anti-B-actin (Santa Cruz Biotechnologies SC-47778) for 1 hour at room temperature. The antibodies were detected using 1:10,000 goat-anti-mouse horseradish peroxidase conjugated antibodies (Santa Cruz Biotechnologies). Western Blotting Luminol Reagent (Santa Cruz Biotechnologies) was used to visualize the bands corresponding to each antibody.
  • Single miRNA/mRNA Expression Using Real-Time Polymerase Chain Reaction (RT-PCR)
  • With 10 ng of RNA per reaction, miRNAs of interest were reverse-transcribed with ABI individual stem-loop primers designed to detect only mature miRNA, and measured by Taqman real-time PCR normalized to the small nucleolar RNA, RNU48. In order to assess mRNA expression using RT-PCR, 1 μg of RNA was reverse-transcribed with the ABI High Capacity cDNA Reverse Transcription kit. Gene expression was measured with exon-spanning Taqman probes, and normalized to beta-2 micro globulin expression.
  • Cell Culture
  • BJAB and H929 were cultured in RPMI (Gibco) supplemented with 10% fetal bovine serum, and U266 was cultured in RPMI supplemented with 15% fetal bovine serum. 293T cells were grown in DMEM media (Gibco) with 10% FBS. All cell lines were grown in 37° C. humidified cell culture incubators with CO2 maintained at 5%.
  • MiRNA Functional Analysis
  • MicroRNA Transfection
  • miRNAs of interest were over-expressed in cell lines of interest by transfecting the appropriate miRNA precursors (Ambion) at 100 nanomoles using Amaxa's Nucleofector system. In particular, BJAB was transfected with Nucleofector solution T, program T-016, U266 with Nucleofector C, program X-005, and H929 with Nucleofector V, program T-001. 1.5 million cells were used per transfection and mixed with appropriate miRNA precursors (Ambion) for a concentration of 100 nM.
  • Statistical Analysis
  • Identifying Differentially Expressed miRNA and mRNA
  • MiRNAs were considered to be differentially expressed if the mean signal was changed at least 2-fold and a false discovery rate (q) was less than 5% using Significance Analysis of Microarrays (SAM) with 1000 permutations. See Tusher et al. Proc Natl Acad Sci USA. 2001; 98:5116-5121.
  • Differentially expressed genes (mRNA) in Naive versus Germinal Center, Germinal Center versus Plasma Cells, and Germinal Center versus Memory Cells comparisons were identified using SAM. Genes that were 2-fold differentially expressed at a false discovery rate (q) less than 1% with 1000 permutations were identified as significantly differentially expressed.
  • Transcription Factors and miRNA Target Genes
  • Transcription factors were identified based on the gene ontology (GO search term “transcription factor”) and matched to the probes of the Affymetrix U133plus 2.0 microarray. Of the total of 938 transcription factor genes thus identified, we selected 364 genes that were differentially expressed in at least one of the B cell stage transitions. We evaluated the breakdown of the differentially expressed transcription factors among miRNA targets versus non targets. The p-values were computed using a chi-square test separately in each B cell stage-transition.
  • B Cell Malignancy Sample Classification
  • The top 50 most differentially expressed miRNAs (P<0.01) in each pair-wise B cell malignancy type comparison were chosen as the initial predictor. Singular value decomposition was applied to reduce the list to 20 most informative miRNAs in each pair-wise comparison. See West et al. Proc Natl Acad Sci USA. 2001; 98:11462-11467. A Bayesian logistic regression was performed in Matlab (Mathworks) using the 20-predictor miRNAs for each pair-wise comparison. Each sample was tested using the microRNA-based predictor in a leave-one-out fashion to determine the accuracy of each prediction. For a sample to be classified as a particular B cell malignancy (or normal) type, it had to be predicted as such in every pair-wise comparison.
  • Normal B Cell Stage Classification of B Cell Malignancies
  • We constructed a Bayesian predictor to distinguish normal naive from germinal center B cells based on the 32 miRNAs depicted in FIG. 1D. We then applied the predictor without optimization to the microarray data generated for GCB DLCBL, Burkitt lymphoma and chronic lymphocytic leukemia to render a Bayesian prediction of lineage; i.e. naive versus germinal center B cell.
  • Western Blot Quantitative Analysis
  • Western blot scans were quantified using NIH ImageJ software. For each experiment, the ratios of protein of interest (LM02, PRDM1) to Actin were determined and mean centered to 100 across the experiment. The average and standard deviation of these values across the three experiments were calculated and displayed relative to the scrambled control expression.
  • Luciferase Indicator Assay Quantitative Analysis
  • Firefly luciferase reporter constructs were created in the pL/SV40/GL3 vector for the LM02 3′UTR and the LM02 3′UTR with the predicted miR-223 binding site mutated, as described below. Mature microRNA expression of a pL/CMV/eGFP vector coding for pri-miR-223 from the 3′UTR of EGFP of the vector was confirmed by Taqman-real time PCR in transfected 293T cells. gl3 activity was normalized in dual luciferase assays to pL/SV40/RLuc, with which it was cotransfected. The PRDM1 3′UTR was also cloned into the pL/SV40/GL3 vector. microRNA expression vectors and their respective seed sequence mutants were created for miR-9-2, miR-30b, and miR-30d.
  • LM02
  • The LM02 3′UTR was PCR-amplified from BJAB cDNA using primers 1 and 2 (SEQ ID NOs: 1 and 2, respectively) and ligated into the XhoI and XbaI sites of the previously described lentiviral vector pL/SV40/GL3, which expresses firefly luciferase. See Tusher et al. Proc Natl Acad Sci USA. 2001; 98:5116-5121. As a control, an LM02 3′UTR mutant was created using mutant PCR primers 3 and 4 and then outer primers 1 and 2. The resulting fragment was also placed into the XhoI and XbaI sites of pL/SV40/GL3. In this LM02 3′UTR mutant, the seed match predicted to bind to nucleotides 2-8 of miR-223 is converted from 5′AACUGAC 3′ to 5′AACAGUC 3′. To create a miR-223 expression vector, a ˜350 nucleotide-long fragment of pri-miR-223, encompassing the pre-miRNA stem loop in its middle, was PCR-amplified from genomic BJAB DNA with primers 6 and 7 (SEQ ID NOs. 6 and 7) and ligated into the XhoI and XbaI sites of the pL/CMV/eGFP vector. This pL/CMV/eGFP vector was generated by ligating a fragment containing the CMV promoter and the EGFP ORF into the BamHI and XhoI sites of the previously described lentiviral backbone pL. See Tusher et al. Proc Natl Acad Sci USA. 2001; 98:5116-5121. The expression of miR-223 from the 3′UTR of EGFP in the resulting vector was confirmed by Taqman real time PCR in transfected 293T cells.
  • For luciferase indicator assays, 293T cells plated in 24 well plates were transfected using FUGENE6 as follows:
  • TABLE 1
    Luciferase indicator assay compositions
    2.5 ng pL/SV40/GL3 2.5 ng pL/SV40/GL3/ 2.5 ng pL/SV40/GL3/
    2.5 ng pL/SV40/RLuc LMO2 LMO2 seed
    0.4 μg pL/CMV/ UTR mut
    eGFP/miR-223 2.5 ng pL/SV40/RLuc 2.5 ng pL/SV40/RLuc
    2.5 ng pL/SV40/GL3 0.4 μg pL/CMV/ 0.4 μg pL/CMV/eGFP/
    2.5 ng pL/SV40/RLuc eGFP/miR-223 miR-223
    0.4 μg pL/CMV/eGFP 2.5 ng pL/SV40/ 2.5 ng pL/SV40/GL3/
    GL3/LMO2 LMO2 seed
    UTR mut
    2.5 ng pL/SV40/RLuc 2.5 ng pL/SV40/RLuc
    0.4 μg pL/CMV/eGFP 0.4 μg pL/CMV/eGFP
  • Reporter expression was evaluated by dual luciferase assays (Promega) 48 hours post-transfection. Firefly Luciferase (GL3) to internal control Renilla Luciferase (RLuc) ratios from 293T cells transfected with pL/CMV/eGFP/miR-223 were divided by those obtained from 293T transfected with the pL/CMV/eGFP vector control. The average and standard deviation were taken across five experiments for the pL/SV40/gl3 empty, LM02, and LM02 mutant vectors.
  • Firefly Luciferase (GL3) activity readings of the PRDM1 3′UTR construct were divided by internal control Renilla Luciferase (RLuc) activity readings. The average and standard deviation of these ratios across three experiments were calculated and scaled relative to the empty vector (pL/CMV/eGFP) transfection.
  • TABLE 2
    LM02 primer sequences
    Primer
    SEQ ID description Sequence (5′ → 3′)
    1543 LMO2 3′UTR, FW ATATCTCGAGGCCCGAGTCCCCGGGCATCTTTGG
    1544 LMO2 3′UTR, REV ATATATCTAGACTACACACGACAAATACTTTG
    1545 LMO2 3′UTR seed CAGCCCATCCATAGTAACAGTCATGATTAGCAGAAGAAAGG
    mutant, FW
    1546 LMO2 3′UTR seed CCTTTCTTCTGCTAATCATGACTGTTACTATGGATGGGCTG
    mutant, REV
    1547 pri-mir-223, FW ATATCTCGAGGGTCACATCTCCCAGGAAGATC
    1548 pri-mir-223, REV ATATATCTAGAAGCACTCTCATGGTGTGTGTAG
  • PRDM1
  • The PRDM1 3′UTR was PCR-amplified from BJAB genomic DNA in two reactions using primer pairs 7 and 8 in one reaction, and 9 and 10 in another (SEQ ID NOs: 7 to 10, respectively). The two fragments were then ligated together into the XhoI and NotI sites of pL/SV40/GL3 to generate the entire PRDM1 3′UTR. microRNA expression vectors were created as described above for mir-9-2, mir-30b, and mir-30d with the primers listed below. Again, over-expression from the 3′UTR of EGFP in the resulting vector was confirmed by Taqman real-time PCR in transfected 293T cells. For the PRDM1 luciferase assays, we used the sequences listed below to PCR-mutate the seed sequence of the microRNA expression vectors rather than the PRDM1 3′UTR, which had numerous seed sequence binding sites.
  • TABLE 3
    PRDM1 primer sequences
    Primer
    SEQ ID: description sequence
    1549 PRDM1 3′UTR piece 1, FW AGAGACTCGAGGATTTTCAGAAAACACTTATTT
    1550 PRDM1 3′UTR piece 1, REV TTGCTTCTCTAGAGGAGAAAC
    1551 PRDM1 3′UTR piece 2, FW GTTTCTCCTCTAGAGAAGCAA
    1552 PRDM1 3′UTR piece 2, REV AGAGAGCGGCCGCAGGGGAGAGACAAATTGCATTG
    1553 pri-mir-9-2, FW AGAGACTCGAGATAAAAGGAGGAATCTTAAG
    1554 pri-mir-9-2, REV AGAGAGCGGCCGCGAAAAAAACAAAACAAAAACAA
    1555 pri-mir-30b, FW AGAGAGCGGCCGCCCGATTGAGTCTTGCCTCAT
    1556 pri-mir-30b, REV AGAGAGAATTCAATGGTCTCACATTTCCAAC
    1557 pri-mir-30d, FW AGAGAGCGGCCGCATGTCACAGCTATTGTTCAG
    1558 pri-mir-30d, REV AGAGAGAATTCGCAGTAAAAGAATGCAGCTA
    1559 pri-mir-9-2 seed mutant, FW GGAAGCGAGTTGTTATCTATGCTTATCTAGCTGTATGAGT
    1560 pri-mir-9-2 seed mutant, REV ACTCATACAGCTAGATAAGCATAGATAACAACTCGCTTCC
    1561 pri-mir-30b seed mutant, FW ACCAAGTTTCAGTTCATGTTAAGATCCTACACTCAGCTGT
    1562 pri-mir-30b seed mutant, REV ACAGCTGAGTGTAGGATCTTAACATGAACTGAAACTTGGT
    1563 pri-mir-30d seed mutant, FW CAGAAAGTCTGTTGTTGTTAAGATCCCCGACTGGAAGCTG
    1564 pri-mir-30d seed mutant, REV CAGCTTCCAGTCGGGGATCTTAACAACAACAGACTTTCTG
  • Luciferase assays were carried out in a manner similar to those described for LMO2.
  • IgVH Mutation Status of Chronic Lymphocytic Leukemia Samples
  • IgVH mutation status was determined as described in Volkheimer et al. (Blood. 2007; 109:1559-1567) using genomic DNA. In brief, genomic DNA was isolated from purified CLL cells and isolated using the GenElute Mammalian DNA extraction Kit from Sigma (St. Louis, Mo.) according to the manufacturer's instructions. DNA was amplified using nested PCR primers. PCR products were electrophoresed, purified, and sequenced using an automated DNA sequencer (Applied Biosystems, Foster City, Calif.) with the BigDye Terminator kit (Perkin Elmer, Boston, Mass.). Forward and reverse sequences were aligned into a single resolved sequence using Sequencher 4.1 software (Gene Codes Corporation, Ann Arbor, Mich.), and then aligned with germline sequences derived from DNA Plot on the V BASE directory website (http://vbase.mrc-cpe.cam.ac.uk/). The percent sequence identity was calculated by dividing the number of mutations from FR1 to FR3 by the total number of nucleotides in this region. Samples were considered somatically mutated if they had greater than 2% mutations in this region.
  • Example 2 Mature B Cell Stages Display Characteristic Patterns of MicroRNA Expression
  • Mature B cell subsets can be defined by the expression of surface CD19, IgD, CD38, and CD27, and were obtained by fluorescence activated cell sorting of tonsils from young individuals undergoing routine tonsillectomy. See FIGS. 1B and 1C. Cells were previously gated on CD19 positive cells. Naive and memory B cells were distinguished from germinal center and plasma cells based on surface CD38 and IgD expression.
  • To determine whether mature B cell subsets had unique patterns of microRNA (miRNA) expression, we used a 384-well multiplexed real time polymerase chain reaction (RT-PCR) assay (Applied Biosystems) that allowed measurement of all 365 miRNAs in miRBase 9.2. See Chen et al. Nucleic Acids Res. 2005; 33:e179; and He et al. Nature. 2007; 447:1130-1134. We detected a total of 113 unique miRNAs in the B cell populations. See Table 4. This detection frequency compares favorably to the identification of 71 unique miRNAs (45 miRNAs with more than one clone) through the examination of 3101 sequences cloned from unselected CD19-positive mature B cells. See Landgraf et al. Cell. 2007; 129:1401-1414. We identified differentially expressed miRNAs in mature B cell subsets using a false discovery rate of less than 5%. See FIGS. 1D, 1F, and 1H. The complete list of assayed miRNAs found to be expressed in the B cell populations is shown in Tables 4 and 5.
  • In Table 4, normalized expression values for B-cell subsets are shown, along with significance analysis of microarrays q values. Empty microRNA expression cells indicate below-threshold values, defined as RT-QPCR Ct values greater than 36 or undetected. SAM q values greater than 5 were considered non-significant and not displayed.
  • TABLE 4
    MicroRNAs detected in at least one B-cell subset
    qNaive qGerminal qGerminal
    Germinal vs Center Center
    Naïve Center Plasma Cell Memory Germinal vs vs
    average average average average Center Plasma Cell Memory
    hsa-let-7a 11.7 9.2 11.2 1.4
    hsa-let-7b 10.3 9.0 7.7 11.3 0.0
    hsa-let-7c 7.3 7.2
    hsa-let-7d 9.0 9.0 10.0
    hsa-let-7f 10.3 7.6 8.4 10.2 0.0
    hsa-let-7g 13.1 10.3 10.5 14.0 0.0 0.0
    hsa-miR-100 7.4
    hsa-miR-101 8.4 10.0
    hsa-miR-103 9.7 11.4 9.8 10.8 0.0 0.0
    hsa-miR-106b 11.7 12.5 11.6 12.7
    hsa-miR-125a 6.7 8.3
    hsa-miR-125b 6.3 7.3
    hsa-miR-130b 7.8 9.8 8.6 10.2 3.6 4.5
    hsa-miR-132 7.5 8.9
    hsa-miR-133b 7.7 7.7 7.2 7.3
    hsa-miR-140 10.8 12.0 11.1 12.0 4.7
    hsa-miR-141 7.0 6.2
    hsa-miR-142-3p 16.9 17.0 15.3 18.0 1.1
    hsa-miR-142-5p 11.7 11.0 9.8 13.4 2.1
    hsa-miR-146a 10.1 14.0 14.0 14.6 0.0
    hsa-miR-146b 9.2 9.2 8.1 10.5 2.1
    hsa-miR-148a 6.7 9.4 11.9 9.0 0.0
    hsa-miR-148b 6.4 8.5
    hsa-miR-151 8.2 9.6 6.6 9.0 1.5 0.0
    hsa-miR-152 6.4 9.7 6.6
    hsa-miR-155 14.2 14.6 15.0 15.6
    hsa-miR-15a 10.2 10.1 7.8 10.8 2.0
    hsa-miR-15b 11.2 14.0 12.6 12.9 0.0 2.8
    hsa-miR-16 16.7 17.3 17.1 17.1
    hsa-miR-17-3p 9.1
    hsa-miR-17-5p 8.8 11.5 8.9 9.4 0.0 0.0 0.0
    hsa-miR-181b 9.0 11.7 10.8 9.3 0.0 0.0
    hsa-miR-181d 8.2 10.6 8.5 9.0 0.0 1.1
    hsa-miR-182 8.7 8.7
    hsa-miR-186 8.8 9.2 8.7 9.7
    hsa-miR-18a 5.7 8.9 6.8 7.4 0.0 0.0
    hsa-miR-191 11.9 12.7 12.4 13.3
    hsa-miR-192 9.1 9.0 8.8 10.1
    hsa-miR-193b 6.6
    hsa-miR-194 6.8 7.4 4.9 9.5 2.0 4.7
    hsa-miR-195 10.3 8.7 8.8 9.2
    hsa-miR-197 9.7 10.5 8.7 11.0 0.0
    hsa-miR-199a* 7.0
    hsa-miR-19a 9.7 12.8 11.9 11.1 0.0
    hsa-miR-19b 14.0 15.6 14.9 15.0 0.8
    hsa-miR-200a 6.5 6.8
    hsa-miR-200b 7.5
    hsa-miR-200c 9.0 9.6 9.7
    hsa-miR-203 7.9 7.6
    hsa-miR-20a 12.5 14.9 12.2 13.8 0.0 0.0
    hsa-miR-20b 8.4 11.0 8.0 8.5 0.0 1.1 0.0
    hsa-miR-21 12.6 13.0 11.2 15.1 2.8 2.1
    hsa-miR-210 9.2 11.1 10.7 10.2 0.8
    hsa-miR-214 7.6
    hsa-miR-22 8.3 7.4
    hsa-miR-221 6.9
    hsa-miR-222 11.4 11.6 7.8 12.7 0.0 4.7
    hsa-miR-223 13.7 10.4 9.6 14.6 0.0 0.0
    hsa-miR-23a 8.7
    hsa-miR-23b 6.2
    hsa-miR-24 11.7 11.8 12.8 13.4 2.1
    hsa-miR-25 9.7 10.8 8.8 11.2 2.8
    hsa-miR-26a 14.7 13.6 14.2 16.3 0.0
    hsa-miR-26b 12.6 12.1 12.0 14.1 3.4
    hsa-miR-27a 6.5 11.1 0.0
    hsa-miR-27b 7.2
    hsa-miR-28 9.4 13.3 8.4 10.3 0.0 0.0 0.0
    hsa-miR-296 6.9 8.1 6.6 7.9 0.0 2.0
    hsa-miR-29a 13.4 11.7 13.5 15.0 0.0
    hsa-miR-29c 11.2 8.7 12.3 13.3 1.5 2.6 0.0
    hsa-miR-301 6.0 9.6 7.7 7.9 0.0 0.0
    hsa-miR-30a-3p 8.2
    hsa-miR-30a-5p 11.9 12.6 11.3 13.0 2.0
    hsa-miR-30b 11.7 12.6 11.2 13.0 2.8
    hsa-miR-30c 13.0 13.9 12.7 14.3 4.5
    hsa-miR-30d 10.8 11.9 10.1 12.1 3.8 0.0
    hsa-miR-30e-3p 8.3 9.0 6.8 9.9 0.0
    hsa-miR-30e-5p 12.5 8.1 10.2 14.8 0.0
    hsa-miR-31 9.0
    hsa-miR-32 8.4 7.0 10.5
    hsa-miR-320 10.1 8.2 10.3 10.5 1.5 2.6 0.0
    hsa-miR-324-3p 8.8 9.9 9.0 9.5
    hsa-miR-324-5p 8.0 7.8
    hsa-miR-328 8.1 8.6 7.4 8.7 2.8
    hsa-miR-331 9.4 12.6 12.0 10.8 0.0 2.6
    hsa-miR-335 6.3 6.9
    hsa-miR-339 7.3 5.7 8.9
    hsa-miR-342 12.7 12.5 10.6 13.1 0.0
    hsa-miR-345 6.8 7.1 7.8 8.6 3.4
    hsa-miR-361 8.3
    hsa-miR-365 6.0 7.8 8.3 8.4 0.0
    hsa-miR-374 8.0 8.9 10.4 9.8
    hsa-miR-423 8.0 9.7 7.6 8.7 0.0 0.0
    hsa-miR-425 6.9
    hsa-miR-425-5p 8.7 11.6 9.7 10.2 0.0 0.0
    hsa-miR-484 11.5 12.3 12.9 12.0
    hsa-miR-486 7.0 8.8 9.9 9.6 3.8
    hsa-miR-532 7.0 7.8
    hsa-miR-545 5.5 6.3
    hsa-miR-572 7.7 6.8
    hsa-miR-629 6.7 7.3 7.2 9.0 1.4
    hsa-miR-646 6.0 7.3
    hsa-miR-650 8.8 11.4 8.0
    hsa-miR-659 7.6 6.0 6.8
    hsa-miR-660 9.5 8.6 10.1
    hsa-miR-7 6.1 5.8
    hsa-miR-9 7.8 6.8 6.2 2.8
    hsa-miR-9* 6.4 6.5
    hsa-miR-92 14.5 15.8 14.2 15.5 3.6 0.0
    hsa-miR-93 11.5 14.6 10.5 12.3 0.0 0.0 0.0
    hsa-miR-98 6.3 5.0 5.0 7.8 2.1
    hsa-miR-99a 7.3
    hsa-miR-99b 6.8
  • TABLE 5
    miRNAs measured using the multiplex RT-PCR assay, but not consistently
    detected in any B-cell population
    hsa-let-7e hsa-miR-383 hsa-miR-376a hsa-miR-566
    hsa-miR-I0a hsa-miR-198 hsa-miR-376b hsa-miR-551b
    hsa-miR-I0b hsa-miR-224 hsa-miR-380-5p hsa-miR-569
    hsa-miR-34a hsa-miR-299-5p hsa-miR-410 hsa-miR-570
    hsa-miR-34b hsa-miR-409-5p hsa-miR-412 hsa-miR-548a
    hsa-miR-34c hsa-miR-432 hsa-miR-432 hsa-miR-586
    hsa-miR-107 hsa-miR-433 hsa-miR-512-5p hsa-miR-587
    hsa-miR-181c hsa-miR-485-5p hsa-miR-199a hsa-miR-548b
    hsa-miR-215 hsa-miR-489 hsa-miR-199b hsa-miR-588
    hsa-miR-218 hsa-miR-494 hsa-miR-219 hsa-miR-589
    hsa-miR-372 hsa-miR-506 hsa-miR-323 hsa-miR-550
    hsa-miR-375 hsa-miR-508 hsa-miR-338 hsa-miR-591
    hsa-miR-378 hsa-miR-521 hsa-miR-368 hsa-miR-593
    hsa-miR-137 hsa-miR-134 hsa-miR-373 hsa-miR-596
    hsa-miR-200a hsa-miR-147 hsa-miR-373 hsa-miR-597
    hsa-miR-I hsa-miR-149 hsa-miR-382 hsa-miR-622
    hsa-miR-183 hsa-miR-153 hsa-miR-424 hsa-miR-599
    hsa-miR-302a hsa-miR-187 hsa-miR-448 hsa-miR-600
    hsa-miR-302c hsa-miR-190 hsa-miR-450 hsa-miR-624
    hsa-miR-302d hsa-miR-193a hsa-miR-451 hsa-miR-601
    hsa-miR-367 hsa-miR-196a hsa-miR-452 hsa-miR-626
    hsa-miR-369-5p hsa-miR-196b hsa-miR-452 hsa-miR-548d
    hsa-miR-449 hsa-miR-205 hsa-miR-453 hsa-miR-639
    hsa-miR-497 hsa-miR-208 hsa-miR-485-3p hsa-miR-613
    hsa-miR-501 hsa-miR-213 hsa-miR-488 hsa-miR-614
    hsa-miR-509 hsa-miR-220 hsa-miR-490 hsa-miR-615
    hsa-miR-510 hsa-miR-325 hsa-miR-492 hsa-miR-616
    hsa-miR-511 hsa-miR-326 hsa-miR-493 hsa-miR-548c
    hsa-miR-514 hsa-miR-337 hsa-miR-503 hsa-miR-617
    hsa-miR-515-3p hsa-miR-340 hsa-miR-504 hsa-miR-642
    hsa-miR-515-5p hsa-miR-380-3p hsa-miR-505 hsa-miR-618
    hsa-miR-517a hsa-miR-422b hsa-miR-507 hsa-miR-644
    hsa-miR-517b hsa-miR-422a hsa-miR-513 hsa-miR-647
    hsa-miR-517c hsa-miR-429 hsa-miR-516-5p hsa-miR-649
    hsa-miR-518a hsa-miR-491 hsa-miR-517 hsa-miR-661
    hsa-miR-518b hsa-miR-496 hsa-miR-518c hsa-miR-662
    hsa-miR-518c hsa-miR-500 hsa-miR-518f hsa-miR-449b
    hsa-miR-518d hsa-miR-502 hsa-miR-519b hsa-miR-653
    hsa-miR-518e hsa-miR-105 hsa-miR-519c hsa-miR-411
    hsa-miR-520a hsa-miR-122a hsa-miR-519d hsa-miR-654
    hsa-miR-520b hsa-miR-124a hsa-miR-51ge hsa-miR-575
    hsa-miR-520c hsa-miR-126 hsa-miR-522 hsa-miR-576
    hsa-miR-520d hsa-miR-128b hsa-miR-523 hsa-miR-578
    hsa-miR-520e hsa-miR-129 hsa-miR-524 hsa-miR-579
    hsa-miR-520f hsa-miR-130a hsa-miR-526b hsa-miR-580
    hsa-miR-520g hsa-miR-139 hsa-miR-96 hsa-miR-585
    hsa-miR-520h hsa-miR-143 hsa-miR-651 hsa-miR-
    512-3p
    hsa-miR-95 hsa-miR-145 hsa-miR-376a hsa-miR-631
    hsa-miR-126 hsa-miR-182 hsa-miR-542-5p hsa-miR-363
    hsa-miR-127 hsa-miR-185 hsa-miR-544 hsa-miR-487b
    hsa-miR-133a hsa-miR-189 hsa-miR-656 hsa-miR-645
    hsa-miR-135a hsa-miR-18b hsa-miR-549 hsa-miR-556
    hsa-miR-135b hsa-miR-202 hsa-miR-657 hsa-miR-558
    hsa-miR-184 hsa-miR-202 hsa-miR-658 hsa-miR-627
    hsa-miR-204 hsa-miR-299-3p hsa-miR-652 hsa-miR-630
    hsa-miR-206 hsa-miR-302a hsa-miR-551a hsa-miR-603
    hsa-miR-211 hsa-miR-302b hsa-miR-552 hsa-miR-606
    hsa-miR-216 hsa-miR-302b hsa-miR-553 hsa-miR-607
    hsa-miR-217 hsa-miR-302c hsa-miR-554 hsa-miR-608
    hsa-miR-330 hsa-miR-329 hsa-miR-555 hsa-miR-609
    hsa-miR-371 hsa-miR-33 hsa-miR-562 hsa-miR-633
    hsa-miR-379 hsa-miR-362 hsa-miR-563 hsa-miR-565*
    hsa-miR-381 hsa-miR-369-3p hsa-miR-564 hsa-miR-594*
    miRNAs marked with * were not used in analyses because they have been reclassified as non-miRNAs.
  • The B cell subsets were profiled for gene expression at the whole genome level, as described previously. See Dave et al. N Engl J Med. 2004; 351:2159-2169. At each stage, we identified differentially expressed genes as those genes with a mean two-fold difference in expression and a false-discovery rate of less than 1%. See FIGS. 1E, 1G, and 1I. Genes that we found to be differentially expressed in each stage-transition were consistent with previous studies that examined gene expression in B cell subsets using microarrays with fewer probes, an overlap that was found to be highly statistically significant (P<0.001, chi-squared test). See, e.g., Klein et al. Proc Natl Acad Sci USA. 2003; 100:2639-2644; and Shaffer et al. Immunity. 2001; 15: 375-385.
  • In the naïve→germinal center (GC) B cell transition, we identified 32 miRNAs that were differentially expressed. Interestingly, all but 4 miRNAs were found to be expressed more highly in GC cells than in naive B cells. See FIG. 1D. We confirmed the mRNA expression patterns of several genes that are known to be differentially expressed in the transition including BCL6, MME, MYBL1, as well as LM02. See FIG. 1E. LM02 was found to be expressed more highly in germinal center B cells compared to both naive B cells and memory B cells. See FIGS. 1E and 1I. In the GC→plasma cell transition, we found 33 miRNAs that were differentially expressed. Once again, we noted a striking asymmetry, with all but 2 miRNAs found to be expressed highly in GC cells, but down-regulated in plasma cells. See FIG. 1F. We also confirmed that the plasma cell-specific genes, PRDM1 (FIG. 1G), XBP1 and IRF4 were highly differentially expressed in our experiments. In the GC→memory B cell transition, there was a preponderance of the 27 significant miRNAs expressed at higher levels in memory cells, See FIG. 1H. Five miRNAs were expressed highly in GC cells compared to all the other B cell types. These included 3 members of the miR-17˜92 cluster (miR-17-5p, miR-20b, miR-93), as well as miR-28 and miR-181b.
  • The expression pattern of all the miRNAs that were measurable in at least one of the B cell subsets is summarized in FIG. 5. Notably, there were no differences in the expression of genes involved in miRNA processing, including DICER1, DROSHA, XP05 (exportin5), EIF2C2 (ag02) and DGCR8, among the B cell subsets. See FIG. 1J.
  • Separately, we examined the expression of predicted target genes of differentially expressed microRNAs. We also found that predicted mRNA target genes of microRNAs expressed highly in GC cells were expressed at lower levels in GC cells compared to other stages. See FIG. 6 and Appendix A. FIG. 6A shows density plots of the expression frequency of predicted mRNA targets of microRNAs expressed highly in germinal center B cells compared to naive cells. mRNAs from FIG. 1E that were also predicted targets of the miRNAs (N=830) were plotted for both naive cells and germinal center B cells. The depicted p-value was calculated using a 1-sided Kolmogorov-Smirnov test. FIG. 6B shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in germinal center B cells compared to plasma cells. mRNAs from FIG. 1G that were also predicted targets of the miRNAs (N=1098) were plotted for both plasma cells and germinal center B cells. The depicted p-value was calculated using a 1-sided Kolmogorov-Smirnov test. FIG. 6C shows density plots of the expression frequency of predicted mRNA targets of miRNAs expressed highly in the germinal center B cells compared to memory B cells. mRNAs from FIG. 1I that were also predicted targets of the miRNAs (N=269) were plotted for both naive cells and germinal center B cells. The depicted p-value was calculated using a 1-sided Kolmogorov-Smirnov test.
  • In the naïve to germinal center transition (see FIG. 6A), genes with at least a two-fold change in expression were analyzed by SAM using a false discovery rate of less than 1% (Larsson et. al, BMC Bioinformatics. 2005; 6:129), depicted in FIG. 1E. From that list of significantly differentially expressed genes, we determined those that were predicted targets of miRNAs (defined as genes with 3′UTR sequence complementarity to microRNA nucleotides 2-7) that were expressed more highly in germinal center cells. The gene expression distribution of those mRNA targets was graphed for naïve B Cells (blue curve) and germinal center B cells (orange curve). Thus, in FIG. 6A, we show genes differentially expressed between naïve and germinal center B cells that are also predicted targets of miRNA expressed more highly in germinal center B cells. We observe that the expression of these microRNA target genes is lower in germinal center B cells compared to naïve B cells.
  • A similar analysis was carried out for the transitions from germinal center to plasma cell (FIG. 6B) and germinal center to memory cell (FIG. 6C). In all three cases examined, the distribution of germinal center miRNA target gene expression is statistically significantly lower (leftward shift of orange curve), which suggests a possible gene regulatory role for the miRNAs that are more highly expressed in germinal center cells. We note that the observed lower expression of the miRNA target genes could, however, also be caused by other factors such as downstream effects of particular transcription factors. The complete set of genes plotted in FIG. 6 is listed in Appendix A.
  • Finally, we found that a higher proportion of differentially expressed transcription factors are predicted microRNA targets. See FIG. 7. Table 6 shows differentially expressed transcription factors, with the average level of expression for each in naïve, germinal center, plasma, and memory cells. Transcription factors for which the significance analysis showed a q value of 0 are indicated.
  • TABLE 6
    Differentially-expressed transcription factors
    Naïve GC
    Germinal Plasma vs GC vs
    Naïve Center Cell Memory GC: q vs PC: q Mem: q
    ID NAME average average average average value value value
    1 AHR 8.9 10.33 8.36 10.38 0 0
    2 APBB2 6.86 7.87 7.35 6.39 0 0
    3 ARID1A 12.3 12.22 11.11 12.17 0
    4 ARID3A 8.03 6.9 9.81 8.76 0 0 0
    5 ARNTL 9.47 8.4 8.23 9.7 0 0
    6 ATF7 7.83 8.97 8.23 8.44 0
    7 BACH1 10.68 9.97 11.76 10.59 0
    8 BHLHB3 11.11 8.05 13.26 13.26 0 0 0
    9 BPTF 12.23 12.46 11.34 11.86 0
    10 BTG1 15.88 14.95 13.94 15.28 0
    11 CASP8AP2 10.17 10.55 9.44 10.22 0
    12 CBL 11.07 11.69 10.26 11.04 0
    13 CBX4 12.23 12.36 13.69 12.68 0
    14 CCNE1 7.86 9.18 8.87 7.66 0 0
    15 CDH1 5.85 3.85 10.26 4.91 0
    16 CITED2 9.11 9.88 12.56 9.22 0
    17 CLOCK 9.85 7.68 9.91 9.62 0 0 0
    18 CREB5 4.91 5.46 7.24 6.95 0
    19 CREBL1 7.53 6.97 8.06 8.09 0
    20 CREBL2 10.18 9.95 11.1 10.79 0
    21 CSDA 12.12 8.59 10.1 8.98 0 0
    22 DEK 12.73 14.09 10.29 13.15 0 0
    23 DLX2 6.08 4.66 7.04 7.08 0 0
    24 DR1 11.83 11.97 10.65 12.1 0
    25 DTX1 10.98 11.6 10.55 9.62 0 0
    26 DYRK1B 6.32 5.92 7.61 4.96 0
    27 E2F1 7.01 8.37 7.95 7.21 0 0
    28 EGR1 11.92 13.24 13.77 12.75 0
    29 EGR2 10.21 10.43 8.07 10.4 0
    30 EGR3 11.59 9.35 8.24 10.62 0 0 0
    31 ELF1 12.39 12.7 11.34 12.55 0
    32 ELL 7.12 7.83 9.17 7.59 0
    33 ELL2 9.25 8.23 13.6 9.27 0
    34 EPAS1 7.1 7.02 8.39 7.5 0
    35 ETS1 14.25 14.4 12.62 14.17 0
    36 ETS2 6.37 7.5 5.66 4.9 0 0 0
    37 ETV1 8.19 6.9 7.38 7.06 0
    38 ETV4 5.99 5.42 7.15 6.09 0
    39 ETV6 10.36 7.14 8.89 10.43 0 0 0
    40 FHL2 4.82 7.77 6.82 5.65 0 0
    41 FLNA 9.95 9.2 8.57 11.03 0
    42 FOS 12.35 11.25 13.34 11.23 0 0
    43 FOSB 10.13 7.21 11.05 10.79 0 0 0
    44 FOXC1 6.81 5.84 7.39 6.59 0
    45 FOXF2 7.05 4.83 6.37 5.84 0
    46 FOXJ2 10.01 8.38 9.97 9.85 0 0 0
    47 FOXK2 8.94 8.4 9.63 8.71 0
    48 GATA3 8.05 7.76 8.51 9.6 0
    49 GATA6 7.08 5.41 7.59 6.26 0 0
    50 GCN5L2 10.18 8.97 8.9 10.36 0 0
    51 GLI2 6.93 7.26 7.52 6.09 0
    52 GPX3 6.72 5.92 7.61 5.58 0
    53 HCLS1 13.94 14.42 13.12 13.92 0
    54 HIPK2 9.36 8.66 11.04 10.85 0 0
    55 HMGA1 11.26 12.47 10.36 10.86 0 0 0
    56 HMGB1 15.47 16.36 14.98 14.97 0 0
    57 HMGB2 12.96 15.78 12.73 13.36 0 0 0
    58 HOXA1 5.36 7.7 7.23 7.64 0
    59 HOXA5 7.03 8.32 8.36 7.54 0
    60 HOXB4 8.2 7.58 9.27 8.01 0
    61 HOXB9 7.4 6.2 8.41 6.87 0
    62 HOXC11 6.6 6.4 7.88 6.21 0
    63 HOXC8 7.05 5.48 6.88 6.71 0
    64 ID4 6.49 5.93 7.79 6.41 0
    65 ILF3 11.26 11.94 10.71 10.99 0
    66 IRAK1 12.19 11.48 12.8 11.96 0
    67 IRF4 11.16 9.28 13.66 10.51 0 0 0
    68 ISL1 6.98 5.91 7.6 6.11 0
    69 JAZF1 11.93 10.65 7.49 11.31 0 0
    70 JMJD1C 12.34 12.34 11.11 12.56 0
    71 JUN 12.14 9.34 12.7 12.16 0 0 0
    72 JUNB 11.62 9.72 10.84 11.37 0 0
    73 KLF11 8.08 5.94 6.88 8.39 0 0
    74 KLF2 12.61 9.1 11.7 12.61 0 0 0
    75 KLF4 10.04 7.57 9.09 7.49 0 0
    76 KLF5 7.08 5.26 6.14 5.07 0
    77 KLF6 12.06 11.33 9.24 12.40 0 0
    78 KLF7 9.36 8.35 8.88 9.8 0
    79 KLF9 9.47 7.34 6.64 9.27 0 0
    80 LITAF 12.52 10.18 11.82 12.49 0 0 0
    81 LMO1 6.86 4.75 7.16 6.88 0
    82 MAF 8.05 9.95 8.25 10.83 0 0
    83 MAFB 6.58 7.3 8.56 7.29 0
    84 MAML3 8.05 10.85 9.07 7.04 0 0 0
    85 MDFIC 12.06 13.67 13.6 13.08 0
    86 MEIS2 7.45 7.15 7.56 5.29 0
    87 MEN1 10.79 11.33 10.49 10.23 0
    88 MITF 7.51 8.05 8.01 6.41 0
    89 MTF1 10.08 9.92 8.86 10.5 0
    90 MXD1 9.07 7.59 9.62 8.9 0 0 0
    91 MXI1 10.63 7.85 11.1 9.42 0 0 0
    92 MYB 6.97 8.62 5.61 7.99 0 0
    93 MYBL1 9.68 14.13 10.02 9.72 0 0 0
    94 MYBL2 9.07 12.41 9.12 8.52 0 0 0
    95 NAT14 6.62 7.66 7.33 7.63 0
    96 NF1 9.23 10.46 11.21 9.88 0
    97 NFAT5 11.71 12.09 10.72 11.77 0
    98 NFATC4 6.36 7.92 8.96 5.71 0 0
    99 NFIX 8.09 7.43 8.67 7.37 0
    100 NFKB1 11.91 11.9 10.7 11.55 0
    101 NFYC 10.2 10.27 9.03 10.03 0
    102 NR3C2 8.85 5.58 4.91 8.41 0 0
    103 NR6A1 9.1 6.03 6.42 7.62 0 0
    104 NRIP1 11.79 10.3 10.33 11.20 0
    105 PAX3 7.01 5.55 5.01 5.96 0
    106 PHF1 11.85 10.69 12.26 11.45 0 0
    107 POU3F1 6.08 7.52 6.86 7.52 0
    108 POU4F1 5.62 8.85 8.46 7.53 0 0
    109 POU4F2 7.09 5.72 7.21 5.1 0 0
    110 PPARD 11.23 9.98 10.29 10.69 0
    111 PPARG 7.79 7.22 6.74 5.47 0
    112 PPARGC1B 6.89 6.09 6.51 7.91 0
    113 PRDM1 8.49 9.15 14.1 9.33 0
    114 PRDM4 10.48 9.81 9.76 10.83 0
    115 PROX1 7.18 6.38 7.89 5.54 0
    116 RAN 13.46 14.57 12.39 13.78 0 0
    117 RSF1 10.05 9.1 9.56 10.18 0
    118 RUNX1T1 7.37 5.95 6.63 6.34 0
    119 RUNX2 8.75 7.91 10.22 9.75 0 0
    120 RUNX3 11.8 11.13 10.26 12.47 0
    121 RXRA 9.07 7.15 8.81 8.32 0 0 0
    122 SAP30 8.22 9.91 9.28 8.33 0 0
    123 SCMH1 8.48 9.69 9.65 8.62 0 0
    124 SCML1 10.32 8.48 7.81 7.91 0
    125 SCML2 10.33 8.76 9.27 8.96 0
    126 SF1 11.72 11.44 10.36 11.37 0
    127 SIAH2 10.35 12.34 10.57 9.90 0 0 0
    128 SLC2A4RG 8.25 8.98 7.4 8.91 0
    129 SMAD1 5.91 8.1 6.34 7.33 0 0
    130 SMAD2 10.45 11.57 10.8 10.98 0
    131 SMAD3 10.72 9.23 7.74 10.54 0 0 0
    132 SMARCA2 11.14 10.12 10.79 11.19 0 0
    133 SOLH 8.78 7.88 8.7 9.03 0
    134 SOX4 8.99 9.14 9.17 10.2 0
    135 SOX5 9.3 10.47 7.33 9.08 0 0 0
    136 SOX9 6.72 8.42 8.18 7.03 0 0
    137 SP4 11.26 10.14 9.58 11.75 0 0
    138 SRCAP 8.58 8.06 6.96 8.38 0
    139 SREBF1 8.23 8.36 6.56 5.89 0 0
    140 STAT5B 10.35 10.95 9.73 10.7 0
    141 SUFU 7.12 6.03 7.84 7.62 0 0
    142 SUPT16H 11.12 11.35 9.6 10.71 0
    143 SUPT3H 7.77 6.3 8.05 8.35 0 0 0
    144 TARDBP 12.31 12.72 11.49 11.91 0
    145 TBP 10.55 10.14 9.09 10.38 0
    146 TBX3 5.67 6.05 7.89 5.53 0
    147 TCEA1 13.31 15 14.05 13.6 0 0
    148 TCERG1 12.29 12.5 11.46 12.04 0
    149 TCF7 10.21 10.82 9.97 12.61 0
    150 TFAP2A 6.7 5.54 8.26 6.88 0
    151 TFAP4 7.28 5.29 5.42 5.13 0
    152 TFDP1 10.95 12.9 10.49 11.36 0 0 0
    153 TFEB 11.56 11.15 9.49 11.77 0
    154 THRA 7.41 7.26 8.48 7.05 0
    155 THRB 7.45 7.51 6.11 6.29 0 0
    156 TLE1 9.19 7.74 9.63 9.13 0 0 0
    157 TMF1 10.76 9.68 10.71 10.42 0
    158 TSC22D3 13.22 11.26 12.67 13.4 0 0 0
    159 UHRF1 9.23 12.22 8.72 8.96 0 0 0
    160 VEZF1 10.98 11.45 9.94 10.81 0
    161 XBP1 10.1 10.74 15.84 10.65 0
    162 YBX1 14.79 15.31 14.2 14.53 0
    163 YWHAH 8.94 10.82 9.09 9.36 0 0 0
    164 YWHAZ 13.38 13.62 12.61 13.62 0
    165 ZFP36L1 14.07 12.89 10.09 13.87 0 0
    166 ZHX3 8.29 7.76 7.47 6.66 0
    167 ZNF207 12.29 13.51 12.69 12.54 0
    168 ZNF217 11.68 10.77 9.73 11.61 0
    169 ZNF219 6.13 6.11 8.42 6.48 0
    170 ZNF238 13.05 11.27 10.08 12.54 0 0 0
    171 ZNF3 8.86 7.27 8.75 8.89 0 0 0
    172 ZNF367 7.97 10.99 8.04 8.22 0 0 0
    173 ZNF398 10.39 9.28 10.47 10.25 0 0
  • Example 3 MiR-223 Regulates LM02 in the Naive˜Germinal Center and Germinal Center˜Memory Cell Transitions
  • MiR-223 has previously been described as being important in the commitment to myeloid lineage. See Chen et al. Science. 2004; 303:83-86; Johnnidis et al. Nature. 2008; 451:1125-1129. We found miR-223 to be expressed at nearly 8-fold higher levels in both naive and memory cells compared to GC cells. This miRNA has a highly conserved sequence complementarity to the 3 ′UTR of 2 transcription factors that are expressed highly during GC cell differentiation: LM02 (FIG. 2A) and MYBL1 (FIG. 8A). Higher expression of miR-223 in the naive B cell stage could inhibit the untimely expression of these transcription factors until the cell is ready to undergo the germinal center reaction.
  • We evaluated the effects of miR-223 expression on its predicted target gene, LM02, by transfecting precursors of miR-223 into a cell line derived from GC cell lymphoma cells (B1AB). Over-expression of miR-223 resulted in a consistent down-regulation of LM02 at the transcript level compared to a transfection with a scrambled control with no sequence complementarity to the human genome. See FIG. 2B. In that figure, the blue bars depict expression of LM02 24 hours after transfection with a scrambled control that does not possess complementarity to the human genome. The orange bars depict the expression of LM02 24 hours after transfection with a precursor for miR-223. The expression of LM02 was consistently lower in the cells treated with the miR-223 precursor, and the results were statistically significant (P<0.05 in all cases, student's t-test). There was no effect on the expression of a non-target control, beta-2 micro globulin in these experiments (data not shown). Over-expression of miR-223 also resulted in a consistent down-regulation of LM02 at the protein level compared to a transfection with a scrambled control with no sequence complementarity to the human genome. See FIG. 2C. We quantified the results of 3 separate experiments examining LM02 protein expression and found consistent down-regulation of LM02 in cells treated with miR-223 compared to cells transfected with scrambled controls. See FIG. 2D. Those results that were statistically significant (P<0.05, student's t-test). The extent of down-regulation of LM02 mRNA and protein by miR-223 was comparable, suggesting that miR-223 regulation of LM02 occurs predominantly at the mRNA level. Similarly, over-expression of miR-223 resulted in a down-regulation of MYBL1 transcripts. See FIG. 8B. In that figure, the blue bars depict expression of MYBL1 mRNA 24 hours after transfection with a scrambled control that does not possess complementarity to the human genome. The orange bars depict the expression of Mybl1 24 hours after transfection with a precursor for miR-223. The expression of LM02 was consistently lower in the cells treated with the miR-223 precursor (P<0.05 in all cases).
  • As additional validation, we investigated whether the miR-223 had a direct effect on LM02 by cloning the 3′UTR sequence of LM02 3′ to the firefly luciferase ORF (Fluc). See Gottwein et al. Nature. 2007; 450:1096-1099. The resulting constructs and the unmodified vector were co-transfected into 293T cells along with a Renilla luciferase internal control and pL-CMV-eGFP constructs expressing either no miRNA or miR-223. Fluc expression from constructs bearing LM02 3′ UTR sequences were differentially down-regulated by miR-223 compared to those with mutated seed sequences; the seed sequence mutant construct had consistently diminished miR-223 repression compared to the wild-type construct in 5 separate experiments. See FIG. 2E. Those results were statistically significant (P<0.05, student's t-test). These observations provide evidence for an inhibitory role for miR-223 in regulating the transcription factor LM02.
  • Activation of LM02 has been associated with the development of leukemia in patients undergoing gene therapy. Hacein-Bey-Abina et al. Science. 2003; 302:415-419. On the other hand, higher expression of PRDM1 alone is sufficient to induce plasma cell-differentiation. Turner et al. Cell. 1994; 77:297-306. Inappropriate expression of such genes must be effectively turned off for a cell to maintain its state. This mode of regulation is reflected in the effects of miR-223, miR-9 and miR-30, which turn off the inappropriate expression of LM02 and PRDM1 and might promote state maintenance and inhibition of lymphomagenesis.
  • On the other hand, our data also identify a number of instances in which miRNAs are co-expressed with their predicted targets. It is possible that such interactions within the cell help to stabilize a defined expression level by dampening fluctuations. For example, in GC cells, we found that miR-181b was strongly co-expressed with its predicted target, BCL6. Such interactions could also be important in B cell stage maintenance and curbing the oncogenic potential of genes involved in B cell differentiation. See Cattoretti et al. Cancer Cell. 2005; 7:445-455; Dorsett et al. Immunity. 2008; 28:630-638.
  • Example 4 MiR-9 and the miR-30 Family Regulate PRDM1 (blimp-1) in the Germinal Center→Plasma Cell Transition
  • In the GC→plasma cell transition, we observed that several members of the miR-30 family were expressed at 2-fold or higher levels in GC cells. See FIG. 1F. The transcription factor PRDM1 is an essential regulator of plasma cell differentiation. Martins et al. Annu Rev Immunol. 2008; 26:133-169. The miR-30 family comprises 5 members (miR-30a, 30b, 30c, 30d and 30e), of which 4 (all except 30e) were found to be expressed at higher levels in GC cells compared to plasma cells. Control transfection experiments documented good specificity of the RT-PCR probes for individual members of the miR-30 family with no discernible cross-hybridization. See FIG. 9. Three separate transfection experiments using high concentrations of miR-30b precursors are shown in the left panel with measurement of miR-30b and miR-30d. Similar experiments were performed with precursors for miR-30d (right panel).
  • The 3′UTR of PRDM1 contains 3 highly conserved binding sites complementary to the seed sequence of members of the miR-30 family, as well as 3 binding sites for the seed sequence of miR-9, 2 of which are highly conserved across multiple species. See FIG. 3A. The 3′UTR region of PRDM1 complementary to miR-30 is shown in red. The 3 sites are complementary to nucleotides 2-8 (UTR position 408), nucleotides 1-8 (UTR position 2370) and nucleotides 2-8 (UTR position 2383) on the miRNA, respectively. The 3′UTR region of PRDM1 complementary to miR-9 is shown in green. The 3 sites are complementary to nucleotides 1-7 (UTR position 1459), nucleotides 2-8 (UTR position 2108) and nucleotides 2-8 (UTR position 2323) on the miRNA respectively. These sites are highly conserved across a number of species, with the exception of one miR-9 site (UTR position 1459) that is only present in humans.
  • To evaluate the effects of the miR-30 family and miR-9 on PRDM1 expression in plasma cells, we introduced precursors of miR-9, miR-30b and miR-30d into the U266 multiple myeloma (plasma cell) cell line. Overexpression of miR-30 family members miR-30b and miR-30d, as well as miR-9, had no effect on PRDM1 at the mRNA level. See FIG. 3B. In that figure, the blue bars depict expression of PRDM1 24 hours after transfection with a scrambled control with no complementarity to the human genome. The magenta bars depict the expression of PRDM1 24 hours after transfection with a hairpin precursor for miR-30b, while the red bars depict the expression of PRDM1 24 hours after transfection with a hairpin precursor for miR-30d. The green bars depict the expression of PRDM1 24 hours after transfection with a hairpin precursor for miR-9. By contrast, there was a consistent down-regulation of PRDM1 at the protein level. See FIGS. 3C and 3D. Those results were statistically significant in each case (P<0.05, student's t-test), except for the transfections with the precursor to miR-9 (P=0.08, student's t-test). Overexpression of each of those microRNAs had an average knockdown effect of around 40%. These exclusively post-transcriptional effects of miR-9 and miR-30 on PRDM1 expression are consistent with one mechanism of miRNA regulation that has been described previously in other systems. See, e.g., O'Donnell et al. Nature. 2005; 435:839-843; Gottwein et al. Nature. 2007; 450:1096-1099; Selbach et al. Nature. 2008; 455:58-63; and Back et al. Nature. 2008; 455:64-71. There was no effect on the expression of a non-target control (Actin).
  • Additionally, luciferase reporter activity of the PRDM1 3′UTR construct was decreased by overexpression of miR-9, miR-30b, and miR-30d, but not their respective seed sequence mutants. See FIG. 3E, which shows the average of three experiments. The down-regulation of the luciferase reporter signal and its restoration in the mutant constructs was found to be statistically significant in each of the 3 microRNAs: miR-9, miR-30b and miR-30d (P<0.05, student's t-test). The luciferase reporter activity level was rescued to the activity level of the empty vector control when the seed sequence of the microRNAs was mutated.
  • The combined effect of 5 different microRNA species (miR-30a, miR-30b, miR-30c, miR-30d and miR-9) is likely to be more potent than that of a single microRNA. The role of mutual repression of BCL6 and PRDM1 in the germinal center to plasma cell differentiation as been described previously. See Martins et al. Immunol. 2008; 26:133-169. Our data suggest that microRNAs may bolster the effects of BCL6 in the inhibition of PRDM1.
  • Our data show that members of the miR-17˜92 family are consistently expressed in GC cells and may play a role in mature B cell differentiation. Interestingly, the miR-17˜92 family has been implicated in early B cell differentiation and mice lacking the loci that encode these miRNAs have arrested early B cell development. See Ventura et al. Cell. 2008; 132:875-886. The expression patterns of the miR-17˜92 family suggest that the regulatory motifs embedded in the interaction of this miRNA family and its targets might have an additional function in regulating mature B cell differentiation.
  • A striking observation in this study is the high degree of asymmetry observed in relative expression of miRNAs in GC cells compared to naive and plasma cells. At least 2 hypotheses could account for these findings. First, miRNA expression may promote a highly regulated state that enables GC cells to interact with T cells and antigen presenting cells, and to leave the GC cells poised for differentiation into memory or plasma cells. Second, miRNAs expressed highly in naive and plasma cells may be underrepresented in current miRNA libraries. Such libraries are often constructed from lymph nodes, which are typically enriched in GC cells. High throughput sequencing of sorted populations of B cells could reveal novel miRNAs that are highly expressed in those populations. Interestingly, a larger number of miRNAs were highly expressed in memory cells compared to GC cells. This observation might stem from the fact that memory cells are known to be heterogeneous (Sanz et al. Semin Immunol. 2008; 20:67-82) and standard methods used to select memory cells may capture a diverse group of memory subpopulations.
  • Example 5 MiRNAs and B Cell Malignancies
  • To examine the expression of B cell stage-specific microRNAs in B cell malignancies, we undertook miRNA profiling of 75 tissue samples derived from normal lymph nodes (N=5) as well as patients with B cell malignancies including the molecular subsets of diffuse large B cell lymphoma (DLBCL; see Rosenwald et al. N Engl J Med. 2002; 346:1937-1947), germinal center B cell-like (GCB) DLBCL (N=20) and activated B cell-like (ABC) DLBCL (N=20), as well as cases of IgV mutated and unmutated chronic lymphocytic leukemia (N=20) and Burkitt lymphoma (N=10).
  • We constructed a Bayesian predictor from miRNAs that distinguished normal memory B cells from GC cells. See FIG. 1H. We tested the predictor in the B cell malignancies derived from germinal center B cells (Burkitt lymphoma and GCB DLBCL) along with chronic lymphocytic leukemia, which is thought to arise from memory B cells. See Klein et al. J Exp Med. 2001; 194:1625-1638. Using leave one out cross-validation, we found that the predictor constructed from miRNAs expressed in normal B cells was able to correctly identify the B cell specific stage of the B cell malignancy type in over 95% of the cases. See FIG. 4A.
  • An interesting aspect regarding the role of miRNAs in malignancies is their reported down-regulation in a number of malignancies compared to normal cells from the same lineage. See Lu et al. Nature. 2005; 435:834-838. To further examine this effect in B cell malignancies, we examined the expression of 113 miRNAs that we had identified in normal B cells. See Table 4, above. Of the 113 miRNAs, 103 were detected using the microarrays that we used to profile B cell malignancies and normal lymph nodes. We applied a 2-sided student's t-test to evaluate the relative expression of those 103 miRNAs in B cell malignancies (N=60) and normal lymph nodes (N=5). 34 miRNAs were differentially expressed (P<0.05) at higher levels in malignant cells and 9 miRNAs were expressed more highly in normal cells. 60 miRNAs were not differentially expressed. See FIG. 4B.
  • As additional validation, we examined miRNA cloning frequencies for sequences cloned from normal and malignant B cells. See Landgraf et al. Cell. 2007; 129:1401-1414. MiRNAs for which a sequence was identified in at least 2 of the 3 available normal B cell samples were used in the analysis. We applied a 2-sided student's t-test (P<0.05) to compare the differential cloning frequency of the miRNAs between normal B cells (N=3) and a variety of mature B cell malignancy patient samples and cell lines (N=42). In all, we found 56 miRNAs that were consistently expressed in normal B cells. We found 13 of those 56 miRNAs were differentially expressed (P<0.05) between normal and malignant B cells, of which 12 miRNAs were expressed more highly in malignant cells and 1 miRNA was expressed more highly in normal cells. See FIG. 4C. In order to avoid effects from tumor-infiltrating non-malignant cells, we repeated the analysis with 20 chronic lymphocytic leukemia samples in the malignant group. The results were similar to those obtained with the larger set of malignancies (data not shown).
  • These results demonstrate that miRNAs are not down-regulated in B cell malignancies compared to normal B cells and that normal B cell stage-specific miRNAs are maintained in B cell malignancies.
  • MicroRNA profiling also revealed that each B cell malignancy type had a distinctive pattern of miRNA expression. See FIG. 4D. In order to evaluate the ability of miRNA profiles to distinguish different B cell malignancy types, we constructed Bayesian predictors from the most highly differentially expressed miRNAs for each pair-wise comparison. See Tables 7, 8, and 9.
  • TABLE 7
    Predictor microRNAs that distinguish germinal center B-cell (GCB)
    DLBCL from Burkitt Lymphoma, activated B-cell (ABC) DLBCL, and
    chronic lymphocytic leukemia
    GCBvsBL GCBvsABC GCBvsCLL
    hsa-miR-146a hsa-miR-142-3p hsa-miR-126
    hsa-miR-154 hsa-miR-16 hsa-miR-130a
    hsa-miR-155 hsa-miR-184 hsa-miR-I0b
    hsa-miR-184 hsa-miR-191 hsa-miR-154
    hsa-miR-29b hsa-miR-19a hsa-miR-193b
    hsa-miR-29c hsa-miR-19b hsa-miR-199a-3p
    hsa-miR-363 hsa-miR-299-5p hsa-miR-365
    hsa-miR-503 hsa-miR-32 hsa-miR-99b
    hsa-miR-519c-5p hsa-miR-30e* hsa-miR-143
    hsa-miR-301a hsa-miR-151-5p hsa-miR-585
    hsa-miR-152 hsa-miR-583 hsa-miR-193a-5p
    hsa-miR-30b* mghv-miR-MI-7-5p hsa-miR-886-5p
    hsa-miR-590-5p hsa-miR-142-5p hsa-miR-I00
    hsa-miR-149* hsa-miR-106b hsa-miR-768-5p
    hsa-miR-300 hsa-miR-30e hsa-miR-145
    hsa-miR-625* hsa-miR-140-3p hsa-miR-943
    kshv-miR-K12-3 hsa-miR-20a hsa-miR-371-5p
    hsa-miR-28-5p hsa-miR-526b* hsa-miR-675
    hsa-miR-25* hsa-miR-28-5p hsa-miR-150
    ebv-miR-BHRFI-2 hsa-miR-30c hsa-miR-181a
    BL = Burkitt lymphoma,
    ABC = activated B-cell DLBCL,
    CLL = chronic lymphocytic lymphoma
  • TABLE 8
    Predictor microRNAs that distinguish activated B-cell (ABC) DLBCL
    from Burkitt Lymphoma and chronic lymphocytic leukemia
    ABCvsBL ABCvsCLL
    hsa-miR-182 hsa-miR-193b
    hsa-miR-377 hsa-miR-99b
    hsa-miR-660 hsa-miR-551a
    hsa-miR-595 mghv-miR-MI-7-3p
    ebv-miR-BARTI0 hsa-miR-585
    hsa-miR-532-5p hsa-miR-617
    hsa-miR-200c* hsa-miR-629*
    hsa-miR-362-3p hsa-miR-575
    hsa-miR-455-3p kshv-miR-K12-6-5p
    hsa-miR-128 hsa-miR-193a-5p
    hsa-miR-21* hsa-miR-30e
    hsa-miR-589 hsa-miR-296-3p
    hsa-miR-135a* hsa-miR-518b
    hsa-miR-532-3p hsa-miR-492
    hsa-miR-548d-5p hsa-miR-220c
    hsa-miR-652 hsa-miR-326
    hsa-miR-150* hsa-miR-671-5p
    hsa-miR-330-5p hsa-miR-340*
    hsa-miR-339-3p hsa-miR-150
    hsa-miR-502-3p hsa-miR-193b*
    BL = Burkitt lymphoma,
    CLL = chronic lymphocytic lymphoma.
  • TABLE 9
    Predictor microRNAs that distinguish Burkitt lymphoma from chronic
    lymphocytic leukemia
    BLvsCLL
    hsa-miR-130b
    hsa-miR-154
    hsa-miR-155
    hsa-miR-29b
    hsa-miR-29c
    hsa-miR-637
    hsa-miR-658
    hsa-miR-193a-5p
    hsa-miR-886-5p
    hsa-miR-768-5p
    hsa-miR-101
    hsa-miR-933
    hsa-miR-371-5p
    hsa-miR-675
    hsa-miR-150
    hsa-miR-874
    hsa-miR-181a
    hsa-miR-30c
    ebv-miR-BHRFI-2
    hsa-miR-628-3p
    CLL = chronic lymphocytic lymphoma
  • We tested the performance of the predictor using leave-one-out cross-validation applied to the predictors for Burkitt lymphoma, chronic lymphocytic leukemia, activated B-cell diffuse large B-cell lymphoma, and germinal center B-cell DLBCL. For a sample prediction to be correct, it had to be classified correctly in each pair-wise comparison with all remaining entities. We found it to be over 90% accurate in the identification of each entity. See FIG. 10.
  • We next expanded the analysis to include follicular lymphoma and Hodgkin's lymphoma. We included the samples from the earlier study and we undertook miRNA profiling of the following additional samples: normal lymph nodes (N=5) and patients with germinal center B cell-like (GCB) DLBCL (N=10), activated B cell-like (ABC) DLBCL (N=10), chronic lymphocytic leukemia (N=10), Burkitt lymphoma (N=10), follicular lymphoma (N=10), and Hodgkin's lymphoma (N=9). As before, microRNA profiling revealed that each B cell malignancy type had a distinctive pattern of miRNA expression. See FIG. 11.
  • From that data, we identified microRNAs that can be used to distinguish each of the six B cell malignancies analyzed from the other five. Lists of those microRNAs, and whether they are expressed in high levels or low levels relative to the other 5 B cell malignancies, are shown in Tables 10 through 13. In certain embodiments, each of those microRNAs could be used to distinguish one of the six B cell malignancies from the other five. High and low in the table refer to at least a 2 fold difference when compared to other lymphomas and benign lymph nodes.
  • TABLE 10
    Predictor microRNAs that distinguish Burkitt lymphoma, germinal center B-cell
    (GCB) DLBCL, and follicular lymphoma from all other B cell malignancies in the study
    BL vs GCB vs FL vs
    BL miRNA list others GCB miRNA list others FL miRNA list others
    hsa-miR-106a High hsa-miR-93/mmu-miR- High hsa-miR-96/mmu-miR- High
    hsa-miR-17/mmu- High 93/rno-miR-93 96/rno-miR-96
    miR-17/rno-miR-17- hsa-miR-886-3p High hsa-miR-138/mmu-miR- High
    5p/rno-miR-17 hsa-miR-365/mmu-miR- High 138/rno-miR-138
    hsa-miR-628-3p High 365/rno-miR-365 hsa-miR-342-5p/mmu- High
    hsa-miR-193a-5p High hsa-miR-378/mmu-miR- High miR-342-5p/rno-miR-342-
    hsa-miR-371-5p High 378/rno-miR-378 5p
    hsa-miR-20a/mmu- High hsa-miR-320/mmu-miR- High hsa-miR-337-3p High
    miR-20a/rno-miR-20a 320/rno-miR-320 hsa-miR-301a/mmu-miR- High
    hsa-miR-23a/mmu- Low hsa-miR-103/mmu-miR- High 301a/rno-miR-301a
    miR-23a/rno-miR-23a 103/rno-miR-103 hsa-miR-922 High
    hsa-miR-27a/mmu- Low hsa-miR-637 High hsa-miR-744/mmu-miR- High
    miR-27a/rno-miR-27a hsa-miR-148a/mmu- High 744
    hsa-miR-34b/mmu- Low miR-148a hsa-miR-221* High
    miR-34b-3p hsa-miR-199a-3p/hsa- High hsa-miR-215 High
    hsa-miR-21/mmu- Low miR-199b-3p/mmu-miR- hsa-miR-197/mmu-miR- High
    miR-21/rno-miR-21 199a-3p/mmu-miR- 197
    hsa-miR-29a/mmu- Low 199b/rno-miR-199a-3p hsa-miR-92b/mmu-miR- High
    miR-29a/rno-miR-29a hsa-miR-126*/mmu- High 92b/rno-miR-92b
    hsa-let-7b/mmu-let- Low miR-126-5p/rno-miR- hsa-miR-218-2*/mmu- High
    7b/rno-let-7b 126* miR-218-2*/rno-miR-
    hsa-let-7f/mmu-let- Low kshv-miR-K12-6-3p High 218*
    7f/rno-let-7f hsa-miR-125a-5p/mmu- High hsa-miR-636 High
    hsa-miR-29b/mmu- Low miR-125a-5p/rno-miR- hsa-miR-600 High
    miR-29b/rno-miR- 125a-5p kshv-miR-K12-7 High
    29b hsa-miR-551b/mmu- Low hsa-miR-194/mmu-miR- High
    hsa-miR-549 Low miR-551b/rno-miR-551b 194/rno-miR-194
    hsa-miR-374a Low hsa-miR-923 Low hsa-miR-524-5p High
    hsa-miR-513a-5p Low hsa-miR-22*/mmu-miR- High
    hsa-miR-148a/mmu- Low 22*/rno-miR-22*
    miR-148a hsa-miR-34c-5p/mmu- High
    hsa-miR-223/mmu- Low miR-34c/rno-miR-34c
    miR-223/rno-miR-223 hsa-miR-151-3p High
    hsa-miR-138- Low hsa-miR-425/mmu-miR- High
    1*/mmu-miR- 425/rno-miR-425
    138*/rno-miR-138* ebv-miR-BART16 High
    hsa-miR-342- Low hsa-miR-20b* High
    3p/mmu-miR-342- hsa-miR-574-3p/mmu- High
    3p/rno-miR-342-3p miR-574-3p
    hsa-miR-146b- Low hsa-miR-155* High
    5p/mmu-miR- hsa-miR-374b* High
    146b/rno-miR-146b hsa-miR-497/mmu-miR- High
    hsa-miR-195/mmu- Low 497/rno-miR-497
    miR-195/rno-miR-195 hsa-miR-708/mmu-miR- High
    hsa-miR-103/mmu- Low 708/rno-miR-708
    miR-103/rno-miR-103 hsa-miR-92a/mmu-miR- High
    hsa-miR-888* Low 92a/rno-miR-92a
    hsa-miR-363/mmu- Low hsa-miR-361-3p High
    miR-363/rno-miR-363 hsa-miR-513a-3p High
    hsa-miR-140- Low hsa-miR-934 High
    3p/mmu-miR- hsa-miR-363*/rno-miR- High
    140*/rno-miR-140* 363*
    hsa-miR-191/mmu- Low mghv-miR-M1-3 High
    miR-191/rno-miR-191 hsa-miR-129* High
    hsa-miR-768-5p Low hsa-miR-148b/mmu-miR- High
    hsa-miR-222/mmu- Low 148b/rno-miR-148b-3p
    miR-222/rno-miR-222 hsa-miR-493 High
    hsa-miR-668/mmu- Low hsa-miR-151-5p/mmu- High
    miR-668 miR-151-5p/rno-miR-151
    hsa-miR-221/mmu- Low hsa-miR-146b-3p High
    miR-221/rno-miR-221 hsa-miR-886-5p High
    hsa-miR-24-1*/mmu- Low hsa-miR-331-3p/mmu- High
    miR-24-1*/rno-miR- miR-331-3p/rno-miR-331
    24-1* hsa-miR-574-5p/mmu- High
    hsa-miR-29c/mmu- Low miR-574-5p
    miR-29c/rno-miR-29c hsa-miR-424 High
    hsa-miR-146a/mmu- Low hsa-miR-152/mmu-miR- High
    miR-146a/rno-miR- 152/rno-miR-152
    146a hsa-miR-302a/mmu-miR- High
    hsa-miR-154/mmu- Low 302a
    miR-154/rno-miR-154 hsa-miR-181a/mmu-miR- High
    hsa-miR-215 Low 181a/rno-miR-181a
    hsa-miR-487b/mmu- Low hsa-miR-509-5p High
    miR-487b/rno-miR- hsa-let-7d/mmu-let- High
    487b 7d/rno-let-7d
    hsa-miR-155 Low hsa-miR-18b High
    hsa-miR-620 High
    hsa-miR-18a/mmu-miR- High
    18a/rno-miR-18a
    hsa-miR-298 High
    hsa-miR-98/mmu-miR- High
    98/rno-miR-98
    hsa-miR-576-3p High
    hsa-miR-374b/mmu-miR- High
    374/rno-miR-374
    hsa-miR-32* High
    hsa-miR-302d* High
    ebv-miR-BART17-5p High
    hsa-miR-620 High
    hsa-miR-665 High
    hsa-miR-185/mmu-miR- High
    185/rno-miR-185
    hsa-miR-34b/mmu-miR- High
    34b-3p
    hsa-let-7e/mmu-let- High
    7e/rno-let-7e
  • TABLE 11
    Predictor microRNAs that distinguish activated B-cell (ABC) DLBCL
    from all other B cell malignancies in the study
    ABC vs
    ABC miRNA list others
    hsa-miR-126/mmu-miR- High
    126-3p/rno-miR-126
    hsa-miR-125b/mmu-miR- High
    125b-5p/rno-miR-125b-5p
    hsa-miR-145/mmu-miR- High
    145/rno-miR-145
    hsa-miR-22/mmu-miR- High
    22/rno-miR-22
    hsa-miR-21/mmu-miR- High
    21/rno-miR-21
    hsa-miR-199a-3p/hsa-miR- High
    199b-3p/mmu-miR-199a-
    3p/mmu-miR-199b/rno-
    miR-199a-3p
    hsa-miR-24/mmu-miR- High
    24/rno-miR-24
    hsa-miR-143/mmu-miR- High
    143/rno-miR-143
    hsa-miR-23b/mmu-miR- High
    23b/rno-miR-23b
    hsa-miR-23a/mmu-miR- High
    23a/rno-miR-23a
    hsa-miR-142-3p/mmu-miR- High
    142-3p/rno-miR-142-3p
    hsa-let-7a/mmu-let-7a/rno- High
    let-7a
    hsa-miR-146b-5p/mmu- High
    miR-146b/rno-miR-146b
    hsa-miR-27a/mmu-miR- High
    27a/rno-miR-27a
    hsa-miR-30a/mmu-miR- High
    30a/rno-miR-30a
    hsa-miR-27b/mmu-miR- High
    27b/rno-miR-27b
    hsa-let-7c/mmu-let-7c/rno- High
    let-7c
    hsa-miR-921 Low
    ebv-miR-BHRF1-2 Low
    hsa-miR-199a-5p/mmu- Low
    miR-199a-5p/rno-miR-
    199a-5p
    hsa-miR-768-5p Low
    hsa-miR-491-3p Low
    hsa-miR-185/mmu-miR- Low
    185/rno-miR-185
    ebv-miR-BART17-5p Low
    hsa-miR-32* Low
    hsa-miR-335/mmu-miR- Low
    335-5p/rno-miR-335
    hsa-miR-149* Low
    hsa-miR-576-3p Low
    hsa-miR-214/mmu-miR- Low
    214/rno-miR-214
    hsa-miR-184/mmu-miR- Low
    184/rno-miR-184
    hsa-miR-520d-5p Low
    hsa-miR-518c* Low
    hsa-miR-801/mmu-miR-801 Low
    hsa-miR-298 Low
    hsa-miR-634 Low
    hsa-miR-583 Low
    hsa-miR-187* Low
    hsa-miR-30d/mmu-miR- Low
    30d/rno-miR-30d
    hsa-miR-129-5p/mmu-miR- Low
    129-5p/rno-miR-129
    hsa-miR-300 Low
    hsa-miR-620 Low
    hsa-miR- Low
    130b*/mmu-miR-
    130b*
    hsa-miR-20b/mmu- Low
    miR-20b/rno-miR-
    20b-5p
    kshv-miR-K12-3 Low
    hsa-miR-28-3p/rno- Low
    miR-28*
    hsa-miR-557 Low
    hsa-miR-150/mmu- Low
    miR-150/rno-miR-
    150
    hsa-miR-98/mmu- Low
    miR-98/rno-miR-98
    hsa-miR-486- Low
    hsa-miR-518a-
    5p/hsa-miR-527
    hsa-miR-302d* Low
    hsa-miR-516a-5p Low
    hsa-miR-148b/mmu- Low
    miR-148b/rno-miR-
    148b-3p
    hsa-miR-25* Low
    hsa-miR-374b/mmu- Low
    miR-374/rno-miR-
    374
    hsa-miR-638 Low
    hsa-miR-302a/mmu- Low
    miR-302a
    hsa-miR-99b*/mmu- Low
    miR-99b*/rno-miR-
    99b*
    hsa-miR-29c*/mmu- Low
    miR-29c*/rno-miR-
    29c*
    hsa-miR-138/mmu- Low
    miR-138/rno-miR-
    138
    hsa-miR-766 Low
    hsa-miR-488 Low
    hsa-miR-498 Low
    hsa-miR-339- Low
    5p/mmu-miR-339-
    5p/rno-miR-339-5p
    hsa-miR-193b* Low
    hsa-miR-299- Low
    5p/mmu-miR-
    299*/rno-miR-299
    ebv-miR-BART8* Low
    hsa-miR-107/mmu- Low
    miR-107/rno-miR-
    107
    hsa-miR-519e* Low
    hsa-miR-146b-3p Low
    hsa-miR-552 Low
    hsa-miR-509-5p Low
    hsa-miR-574- Low
    5p/mmu-miR-574-
    5p
    hsa-miR-524-5p Low
    mghv-miR-M1-7-5p Low
    hsa-miR-659 Low
    hcmv-miR-UL148D Low
    hsa-miR-92a/mmu- Low
    miR-92a/rno-miR-
    92a
    hsa-miR- Low
    30e*/mmu-miR-
    30e*/rno-miR-
    30e*
    hsa-miR- Low
    183*/mmu-miR-
    183*
    hsa-miR-144* Low
    hsa-miR-574- Low
    3p/mmu-miR-574-
    3p
    hsa-miR-889 Low
    hsa-miR-525-5p Low
    kshv-miR-K12-8 Low
    hsa-miR-32/mmu- Low
    miR-32/rno-miR-
    32
    hsa-miR-938 Low
    hsa-miR-198 Low
    hsa-miR- Low
    186/mmu-miR-
    186/rno-miR-186
    hsa-miR- Low
    18a/mmu-miR-
    18a/rno-miR-18a
    hsa-miR-516b Low
    hsa-miR-625* Low
    hsa-miR-551b* Low
    hsa-miR-885-5p Low
    hsa-miR-891a Low
    hsa-miR- Low
    340/mmu-miR-
    340-5p/rno-miR-
    340-5p
    hsa-let-7d/mmu- Low
    let-7d/rno-let-7d
    hsa-miR-151- Low
    5p/mmu-miR-151-
    5p/rno-miR-151
    hsa-miR-18b Low
    ebv-miR-BHRF1-1 Low
    hsa-miR-510 Low
    hsa-miR-625 Low
    mghv-miR-M1-8 Low
    ebv-miR-BART19- Low
    3p
    hsa-miR-147 Low
    hsa-miR-28- Low
    5p/mmu-miR-
    28/rno-miR-28
    ebv-miR-BART13 Low
    hsa-miR-25/mmu- Low
    miR-25/rno-miR-
    25
    hsa-miR-519d Low
    hsa-miR-361- Low
    5p/mmu-miR-
    361/rno-miR-361
    hsa-miR-331- Low
    3p/mmu-miR-331-
    3p/rno-miR-331
    hsa-miR-423- Low
    3p/mmu-miR-423-
    3p/rno-miR-423
    hsa-miR-93/mmu- Low
    miR-93/rno-miR-
    93
  • TABLE 12
    Predictor microRNAs that distinguish chronic lymphocytic leukemia
    from all other B cell malignancies in the study
    CLL vs
    CLL miRNA list others
    hsa-miR- High
    30e*/mmu-miR-
    30e*/rno-miR-30e*
    hsa-miR-32/mmu- High
    miR-32/rno-miR-32
    hsa-let-7g/mmu- High
    let-7g
    hsa-miR-186/mmu- High
    miR-186/rno-miR-
    186
    hsa-miR-140- High
    5p/mmu-miR-
    140/rno-miR-140
    hsa-miR- High
    196a*/mmu-miR-
    196a*/rno-miR-
    196a*
    hsa-miR- High
    487b/mmu-miR-
    487b/rno-miR-487b
    hsa-miR-150/mmu- High
    miR-150/rno-miR-
    150
    hsa-miR-147 High
    hsa-miR-486- High
    5p/mmu-miR-486
    hsa-miR-144* High
    hsa-miR-154/mmu- High
    miR-154/rno-miR-
    154
    hsa-miR-28- High
    5p/mmu-miR-
    28/rno-miR-28
    hsa-miR-299- High
    5p/mmu-miR-
    299*/rno-miR-299
    hsa-miR-33a/mmu- High
    miR-33/rno-miR-33
    hsa-miR-363/mmu- High
    miR-363/rno-miR-
    363
    hsa-miR-891a High
    hsa-miR-768-5p High
    hsa-miR-361- High
    5p/mmu-miR-
    361/rno-miR-361
    hsa-miR-519d High
    hsa-miR-335/mmu- High
    miR-335-5p/rno-
    miR-335
    hsa-miR-668/mmu- High
    miR-668
    hsa-let-7f/mmu-let- High
    7f/rno-let-7f
    hsa-miR-24- High
    1*/mmu-miR-24-
    1*/rno-miR-24-1*
    hsa-miR-223/mmu- High
    miR-223/rno-miR-
    223
    hsa-miR-140- High
    3p/mmu-miR-
    140*/rno-miR-140*
    hsa-miR-144/mmu- High
    miR-144/rno-miR-
    144
    hsa-miR-638 High
    hsa-miR-30d/mmu- High
    miR-30d/rno-miR-
    30d
    hsa-miR-423- High
    3p/mmu-miR-423-
    3p/rno-miR-423
    hsa-miR-155 High
    hsa-miR-101/mmu- High
    miR-101a/rno-miR-
    101a
    hsa-miR-20b/mmu- High
    miR-20b/rno-miR-
    20b-5p
    hsa-miR-374a High
    hsa-miR-25/mmu- High
    miR-25/rno-miR-25
    hsa-miR-199a- High
    5p/mmu-miR-199a-
    5p/rno-miR-199a-
    5p
    hsa-miR-649 High
    hsa-miR-191/mmu- High
    miR-191/rno-miR-
    191
    hsa-miR-30e/mmu- High
    miR-30e/rno-miR-
    30e
    hsa-miR-107/mmu- High
    miR-107/rno-miR-
    107
    hsa-miR-93/mmu- High
    miR-93/rno-miR-93
    hsa-miR-29c/mmu- High
    miR-29c/rno-miR-
    29c
    hsa-miR-541* High
    hsa-miR-888* High
    hsa-miR-549 High
    hsa-miR-19a/mmu- High
    miR-19a/rno-miR-
    19a
    hsa-miR-342- High
    3p/mmu-miR-342-
    3p/rno-miR-342-3p
    hsa-miR-142- High
    5p/mmu-miR-142-
    5p/rno-miR-142-5p
    hsa-miR-801/mmu- High
    miR-801
    hsa-let-7i/mmu-let- High
    7i/rno-let-7i
    hsa-miR-26a/mmu- High
    miR-26a/rno-miR-
    26a
    hsa-miR-15a/mmu- High
    miR-15a
    hsa-miR-195/mmu- High
    miR-195/rno-miR-
    195
    hsa-miR- High
    106b/mmu-miR-
    106b/rno-miR-106b
    hsa-miR-26b/mmu- High
    miR-26b/rno-miR-
    26b
    hsa-miR-15b/mmu- High
    miR-15b/rno-miR-
    15b
    hsa-miR-222/mmu- High
    miR-222/rno-miR-
    222
    hsa-miR-185/mmu- High
    miR-185/rno-miR-
    185
    hsa-miR-550 High
    hsa-let-7e/mmu- Low
    let-7e/rno-let-7e
    hsa-miR-24/mmu- Low
    miR-24/rno-miR-24
    hsa-miR-30c- Low
    2*/mmu-miR-30c-
    2*/rno-miR-30c-2*
    hsa-miR-765 Low
    mghv-miR-M1-4 Low
    hsa-miR-933 Low
    hsa-miR-620 Low
    hsa-miR-30b* Low
    hsa-miR-658 Low
    hsa-miR-10a/mmu- Low
    miR-10a/rno-miR-
    10a-5p
    hsa-miR-665 Low
    hsa-miR-185* Low
    hsa-miR-503 Low
    hsa-miR-126*/mmu-miR- Low
    126-5p/rno-miR-126*
    hsa-miR-10b/mmu-miR- Low
    10b/rno-miR-10b
    hsa-miR-628-3p Low
    hsa-miR-422a Low
    hsa-miR-193a-5p Low
    hsa-miR-143/mmu-miR- Low
    143/rno-miR-143
    hsa-miR-371-5p Low
    hsa-miR-100/mmu-miR- Low
    100/rno-miR-100
    hsa-miR-365/mmu-miR- Low
    365/rno-miR-365
    hsa-miR-145/mmu-miR- Low
    145/rno-miR-145
    kshv-miR-K12-6-3p Low
    ebv-miR-BART6-3p Low
    hsa-miR-220c Low
    hsa-miR-519c-5p/hsa-miR- Low
    519b-5p/hsa-miR-523*/hsa-
    miR-518e*/hsa-miR-
    522*/hsa-miR-519a*
    hsa-miR-130a/mmu-miR- Low
    130a/rno-miR-130a
    hsa-miR-424 Low
    hsa-miR-483-5p Low
    hsa-miR-193b Low
    hsa-miR-637 Low
    hsa-miR-920 Low
    hsa-miR-488 Low
    ebv-miR-BHRF1-2 Low
    hsa-miR-526b Low
    hsa-miR-126/mmu-miR-126- Low
    3p/rno-miR-126
    hsa-miR-943 Low
    hsa-miR-199a-3p/hsa-miR- Low
    199b-3p/mmu-miR-199a-
    3p/mmu-miR-199b/rno-miR-
    199a-3p
    mghv-miR-M1-3 Low
    hsa-miR-934 Low
    hsa-miR-886-5p Low
    hsa-miR-200b*/mmu-miR- Low
    200b*
    hsa-miR-485-3p/mmu-miR- Low
    485*
    hsa-miR-181a/mmu-miR- Low
    181a/rno-miR-181a
    hsa-miR-125b/mmu-miR- Low
    125b-5p/rno-miR-125b-5p
  • TABLE 13
    Predictor microRNAs that distinguish Hodgkin's lympoma from all
    other B cell malignancies in the study
    HL vs
    HL miRNA list others
    hsa-miR-338- High
    5p/mmu-miR-338-
    5p/rno-miR-338*
    hsa-miR-433/mmu- High
    miR-433/rno-miR-
    433
    hsa-miR-552 High
    hsa-miR-202 High
    hsa-miR-299-3p High
    hsa-miR-509-3-5p High
    hsa-miR-490-5p High
    hsa-miR-508-5p High
    hsa-miR-181a-2* High
    hsa-miR-663 High
    hsa-miR-326/mmu- High
    miR-326/rno-miR-
    326
    hsa-miR-542- High
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    hsa-miR-492 High
    hsa-miR-584 High
    hsa-miR-654-5p High
    ebv-miR-BART20-3p High
    hsa-miR-542- High
    5p/mmu-miR-542-
    5p/rno-miR-542-5p
    ebv-miR-BART9* High
    hsa-miR-124/mmu- High
    miR-124/rno-miR-
    124
    hsa-miR-551a High
    hsa-miR-208a/mmu- High
    miR-208a/rno-miR-
    208
    hsa-miR-220b High
    hsa-miR-615- High
    3p/mmu-miR-615-3p
    hsa-miR- High
    135a*/mmu-miR-
    135a*
    hiv1-miR-H1 High
    hsa-miR-124*/mmu- High
    miR-124*/rno-miR-
    124*
    hsa-miR-502-5p High
    hsa-miR-92b* High
    hsa-miR-518a-3p High
    hsa-miR-377* High
    hsa-miR-125a- High
    3p/mmu-miR-125a-
    3p/rno-miR-125a-3p
    hsa-miR-30c- High
    1*/mmu-miR-30c-
    1*/rno-miR-30c-1*
    hsa-miR-650 High
    hsa-miR-629 High
    hsa-miR-296- High
    3p/mmu-miR-296-
    3p/rno-miR-296
    hsa-miR-425*/mmu- High
    miR-425*
    hsa-miR-514 High
    hsa-miR-519e High
    hsa-miR-938 High
    hsa-miR-340*/mmu- High
    miR-340-3p/rno-
    miR-340-3p
    hsa-miR-657 High
    hsa-miR-9*/mmu- High
    miR-9*/rno-miR-9*
    ebv-miR-BART7* High
    hsa-miR-612 High
    hsa-miR-640 High
    hsa-miR-623 High
    hsa-miR-99b*/mmu- High
    miR-99b*/rno-miR-
    99b*
    hsa-miR-645 High
    hsa-miR-484/mmu- High
    miR-484/rno-miR-
    484
    hsa-miR-376a* High
    hsa-miR-345 High
    hsa-miR-586 High
    hsa-miR-622 High
    hsa-miR-206/mmu- High
    miR-206/rno-miR-
    206
    hcmv-miR-US25-1* High
    hsa-miR-302c* High
    hsa-miR- High
    106b*/mmu-miR-
    106b*/rno-miR-
    106b*
    hsa-miR-500 High
    hsa-miR-890 High
    hsa-miR-10a*/mmu- High
    miR-10a*/rno-miR-
    10a-3p
    kshv-miR-K12-1 High
    hsa-miR-629* High
    hsa-miR-193b* High
    ebv-miR-BHRF1-3 High
    hsa-miR-183/mmu- High
    miR-183/rno-miR-
    183
    hsa-let-7b*/mmu- High
    let-7b*/rno-let-7b*
    hsa-miR-409- High
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    hsa-miR-585 High
    hsa-miR-526b* High
    hsa-miR-337-3p High
    hsa-miR-212/mmu- High
    miR-212/rno-miR-
    212
    hsa-miR-548b-3p High
    hcmv-miR-UL112 High
    hsa-miR-601 High
    hsa-let-7d*/mmu- High
    let-7d*/rno-let-7d*
    hsa-miR-181b/mmu- High
    miR-181b/rno-miR-
    181b
    hsa-miR-195* High
    kshv-miR-K12-5 High
    hsa-miR-500* High
    hsa-miR-24- High
    2*/mmu-miR-24-
    2*/rno-miR-24-2*
    hsa-miR-382/mmu- High
    miR-382/rno-miR-
    382
    ebv-miR-BART8* High
    hsa-miR-125b- High
    2*/rno-miR-125b*
    hsa-miR-194* High
    hsa-miR-297/mmu- High
    miR-297a
    hsa-miR-610 High
    hsa-miR-575 High
    hsa-miR-21* High
    hsa-miR-936 High
    kshv-miR-K12-6-5p High
    hsa-miR-553 High
    hsa-miR-652/mmu- High
    miR-652/rno-miR-
    652
    hsa-miR-877/mmu- High
    miR-877/rno-miR-
    877
    hsa-miR-526a/hsa- High
    miR-520c-5p/hsa-
    miR-518d-5p
    hsa-miR-122* High
    hsa-miR-576-5p High
    mghv-miR-M1-6 High
    hsa-miR-551b* High
    hsa-miR-125b- High
    1*/mmu-miR-125b-
    3p/rno-miR-125b-
    3p
    hsa-miR-137/mmu- High
    miR-137/rno-miR-
    137
    ebv-miR-BART18-3p High
    hsa-miR-452 High
    hsa-miR-23a*/rno- High
    miR-23a*
    hsa-miR-617 High
    hsa-miR-550* High
    hsa-miR-557 High
    hsa-miR-331- High
    5p/mmu-miR-331-
    5p
    hsa-miR-296- High
    5p/mmu-miR-296-
    5p/rno-miR-296*
    mghv-miR-M1-2 High
    ebv-miR-BART6-3p High
    hsa-miR-518b High
    hsa-miR-99b/mmu- High
    miR-99b/rno-miR-
    99b
    hsa-miR-525-5p High
    hsa-miR-589 High
    hsa-miR-7-2* High
    hsa-miR-490- High
    3p/mmu-miR-490
    hsa-miR- High
    150*/mmu-miR-
    150*
    hsa-miR-17*/rno- High
    miR-17-3p
    hsa-miR-509-3p High
    ebv-miR-BHRF1-1 High
    hsa-miR- High
    183*/mmu-miR-
    183*
    hsa-miR-635 High
    hsa-miR- High
    130b/mmu-miR-
    130b/rno-miR-130b
    mghv-miR-M1-8 High
    hsa-miR-887 High
    hsa-miR-210/mmu- High
    miR-210/rno-miR-
    210
    hsa-miR-766 High
    hsa-miR-671- High
    5p/mmu-miR-671-
    5p
    hsa-miR-659 High
    hsa-miR-330- High
    5p/mmu-miR-
    330/rno-miR-330
    hsa-miR-323- High
    3p/mmu-miR-323-
    3p/rno-miR-323
    ebv-miR-BART13 High
    ebv-miR-BART5 High
    hsa-miR-602 High
    hcmv-miR-UL148D High
    hsa-miR-373* High
    hsa-miR-526b High
    hsa-miR-328/mmu- High
    miR-328/rno-miR-
    328
    hsa-miR-874/mmu- High
    miR-874/rno-miR-
    874
    ebv-miR-BART19-3p High
    hsa-miR-595 High
    hsa-miR-889 High
    mghv-miR-M1-7-5p High
    hsa-miR-483-5p High
    hsa-miR- High
    487b/mmu-miR-
    487b/rno-miR-487b
    hsa-miR-675 High
    hsa-miR-220c High
    mghv-miR-M1-7-3p High
    hsa-miR-485- High
    3p/mmu-miR-485*
    hsa-miR-198 High
    hsa-miR-483-3p High
    hcmv-miR-UL70-3p High
    hsa-miR-149/mmu- High
    miR-149
    hsa-miR-516a-5p High
    hsa-miR- High
    145*/mmu-miR-
    145*
    hsa-miR-656 High
    hsa-miR-502-3p High
    hsa-miR-29c*/mmu-miR- High
    29c*/rno-miR-29c*
    hsa-miR-937 High
    hsa-miR-515-5p High
    hsa-miR-153/mmu-miR- High
    153/rno-miR-153
    hsa-miR-519e* High
    hsa-miR-128/mmu-miR- High
    128/rno-miR-128
    hsa-miR-516b High
    hsa-miR-532-5p/mmu-miR- High
    532-5p/rno-miR-532-5p
    kshv-miR-K12-8 High
    hsa-miR-455-3p High
    hsa-miR-27a*/mmu-miR- High
    27a*/rno-miR-27a*
    hsa-miR-510 High
    hsa-miR-505/rno-miR-505 High
    hsa-miR-187* High
    hsa-miR-498 High
    hsa-miR-625 High
    hsa-miR-129-5p/mmu-miR- High
    129-5p/rno-miR-129
    ebv-miR-BHRF1-2 High
    hsa-miR-143* High
    kshv-miR-K12-3 High
    hsa-miR-660 High
    hsa-miR-25* High
    hsa-miR-29a*/mmu-miR- High
    29a*/rno-miR-29a*
    hsa-miR-422a High
    hsa-miR-518a-5p/hsa-miR- High
    527
    hsa-miR-519c-5p/hsa-miR- High
    519b-5p/hsa-miR-
    523*/hsa-miR-518e*/hsa-
    miR-522*/hsa-miR-519a*
    hsa-miR-28-3p/rno-miR-28* High
    hsa-miR-300 High
    hsa-miR-130a/mmu-miR- High
    130a/rno-miR-130a
    hsa-miR-583 High
    hsa-miR-149* High
    hsa-miR-184/mmu-miR- High
    184/rno-miR-184
    hsa-miR-625* High
    hsa-miR-99a/mmu-miR- High
    99a/rno-miR-99a
    hsa-miR-199b-5p High
    hsa-miR-513a-5p High
    hsa-miR-494/mmu-miR- High
    494/rno-miR-494
    mghv-miR-M1-4 High
    hsa-miR-634 High
    hsa-miR-923 High
    hsa-miR-503 High
    ebv-miR-BART2-3p High
    hsa-miR-520d-5p High
    hsa-miR-30b* High
    hsa-miR-30c-2*/mmu-miR- High
    30c-2*/rno-miR-30c-2*
    hsa-miR-658 High
    hsa-miR-921 High
    hsa-miR-423-5p/mmu-miR- High
    423-5p
    hsa-miR-933 High
    hsa-miR-23b/mmu-miR- Low
    23b/rno-miR-23b
    hsa-miR-27b/mmu-miR- Low
    27b/rno-miR-27b
    hsa-miR-550 Low
    hsa-let-7a/mmu-let-7a/rno- Low
    let-7a
    hsa-miR-24/mmu-miR- Low
    24/rno-miR-24
    hsa-miR-451/mmu-miR- Low
    451/rno-miR-451
    hsa-miR-30a/mmu-miR- Low
    30a/rno-miR-30a
    hsa-miR-20b/mmu-miR- Low
    20b/rno-miR-20b-5p
    hsa-miR-26a/mmu-miR- Low
    26a/rno-miR-26a
    hsa-miR-26b/mmu-miR- Low
    26b/rno-miR-26b
    hsa-miR-101/mmu-miR- Low
    101a/rno-miR-101a
    hsa-miR-106b/mmu-miR- Low
    106b/rno-miR-106b
    hsa-miR-16/mmu-miR- Low
    16/rno-miR-16
    hsa-miR-29b/mmu-miR- Low
    29b/rno-miR-29b
    hsa-miR-768-3p Low
    hsa-miR-30e/mmu-miR- Low
    30e/rno-miR-30e
    hsa-miR-106a Low
    hsa-miR-142-5p/mmu-miR- Low
    142-5p/rno-miR-142-5p
    hsa-miR-144/mmu-miR- Low
    144/rno-miR-144
    hsa-miR-17/mmu-miR- Low
    17/rno-miR-17-5p/rno-miR-
    17
    hsa-miR-15b/mmu-miR- Low
    15b/rno-miR-15b
    hsa-miR-30c/mmu-miR- Low
    30c/rno-miR-30c
    hsa-miR-142-3p/mmu-miR- Low
    142-3p/rno-miR-142-3p
    hsa-miR-20a/mmu-miR- Low
    20a/rno-miR-20a
    hsa-miR-30b/mmu-miR- Low
    30b/rno-miR-30b-5p
    hsa-miR-19a/mmu-miR- Low
    19a/rno-miR-19a
    hsa-miR-19b/mmu-miR- Low
    19b/rno-miR-19b
  • From the data in Tables 10 through 13, we identified subsets of microRNAs that are sufficient to distinguish each of the six B cell malignancies from the other five. We selected only microRNAs that are expressed more highly in the selected B cell malignancy. Those microRNAs are listed in Tables 14 and 15. In certain embodiments, each of the microRNAs listed in Tables 14 and 15 can be used to distinguish one B cell malignancy from the other five.
  • TABLE 14
    Predictor microRNAs that distinguish activated B-cell (ABC) DLBCL, germinal
    center B-cell like (GCB) DLBCL, and Burkitt lymphoma
    ABC High GCB High BL High
    hsa-miR-22/mmu-miR-22/rno-miR- hsa-miR-93/mmu-miR-93/rno-miR-93 hsa-miR-628-
    22 hsa-miR-103/mmu-miR-103/rno-miR-103 3p
    hsa-miR-21/mmu-miR-21/rno-miR- hsa-miR-320/mmu-miR-320/rno-miR-320
    21 hsa-miR-125a-5p/mmu-miR-125a-5p/rno-miR-
    hsa-miR-24/mmu-miR-24/rno-miR- 125a-5p
    24
    hsa-miR-23b/mmu-miR-23b/rno-
    miR-23b
    hsa-miR-23a/mmu-miR-23a/rno-
    miR-23a
    hsa-let-7a/mmu-let-7a/rno-let-7a
    hsa-let-7c/mmu-let-7c/rno-let-7c
  • TABLE 15
    Predictor microRNAs that distinguish chromic lymphocytic leukemia, follicular
    lymphoma, and Hodgkin's lymphoma
    CLL High FL High HL High
    hsa-miR-32/mmu-miR-32/rno- hsa-miR-152/mmu-miR- hsa-miR-498
    miR-32 152/rno-miR-152 hsa-miR-525-5p
    hsa-miR-150/mmu-miR-150/rno- hsa-miR-885-5p hsa-miR-551b*
    miR-150 hsv1-miR-H1 hsa-miR-340*/mmu-miR-340-
    hsa-miR-140-5p/mmu-miR- hsa-miR-548d-5p 3p/rno-miR-340-3p
    140/rno-miR-140 hsa-miR-488 hsa-miR-494/mmu-miR-494/rno-
    hsa-let-7g/mmu-let-7g ebv-miR-BART16 miR-494
    hsa-miR-154/mmu-miR-154/rno- hsa-miR-22*/mmu-miR- hsa-miR-183*/mmu-miR-183*
    miR-154 22*/rno-miR-22* hsa-miR-659
    hsa-miR-486-5p/mmu-miR-486 hsa-miR-513a-3p hsa-miR-193b*
    hsa-miR-101/mmu-miR- hsa-miR-708/mmu-miR- hsa-miR-766
    101a/rno-miR-101a 708/rno-miR-708 hsa-miR-516a-5p
    hsa-miR-30e/mmu-miR-30e/rno- hsa-miR-425/mmu-miR- hsa-miR-125b-1*/mmu-miR-
    miR-30e 425/rno-miR-425 125b-3p/rno-miR-125b-3p
    hsa-miR-768-5p hsa-miR-337-3p ebv-miR-BART6-3p
    hsa-miR-363/mmu-miR-363/rno- ebv-miR-BART17-5p ebv-miR-BART8*
    miR-363 hsa-miR-221* hsa-miR-509-3-5p
    hsa-miR-668/mmu-miR-668 hsa-miR-92b/mmu-miR- hsa-miR-602
    hsa-miR-147 92b/rno-miR-92b ebv-miR-BHRF1-1
    hsa-miR-196a*/mmu-miR- hsa-miR-197/mmu-miR-197 mghv-miR-M1-2
    196a*/rno-miR-196a* hsa-miR-32* hsa-miR-145*/mmu-miR-145*
    hsa-miR-142-5p/mmu-miR-142- hsa-miR-342-5p/mmu-miR- hsa-miR-296-5p/mmu-miR-296-
    5p/rno-miR-142-5p 342-5p/rno-miR-342-5p 5p/rno-miR-296*
    hsa-miR-199a-5p/mmu-miR- hsa-miR-524-5p hsa-miR-17*/rno-miR-17-3p
    199a-5p/rno-miR-199a-5p hsa-miR-34c-5p/mmu-miR- hsa-miR-452
    hsa-miR-24-1*/mmu-miR-24- 34c/rno-miR-34c hsa-miR-326/mmu-miR-326/rno-
    1*/rno-miR-24-1* hsa-let-7e/mmu-let-7e/rno-let- miR-326
    hsa-miR-891a 7e hsa-miR-652/mmu-miR-652/rno-
    hsa-miR-550 hsa-miR-151-3p miR-652
    hsa-miR-801/mmu-miR-801 hsa-miR-744/mmu-miR-744 hsa-miR-623
    hsa-miR-549 hsa-miR-574-3p/mmu-miR- hsa-miR-194*
    hsa-miR-888* 574-3p hsa-miR-125a-3p/mmu-miR-
    hsa-miR-600 125a-3p/rno-miR-125a-3p
    hsa-miR-20b* hsa-miR-10a*/mmu-miR-
    hsa-miR-194/mmu-miR- 10a*/rno-miR-10a-3p
    194/rno-miR-194 hsa-miR-519e
    hsa-miR-363*/rno-miR-363* hsa-miR-502-5p
    hsa-miR-155* hsa-miR-124*/mmu-miR-
    hsa-miR-34b/mmu-miR-34b-3p 124*/rno-miR-124*
    hsa-miR-922 hsa-miR-345
    hsa-miR-497/mmu-miR- hsa-miR-584
    497/rno-miR-497 hsa-miR-650
    hsa-miR-493 hsa-miR-202
    hsa-miR-138/mmu-miR- hsa-miR-548b-3p
    138/rno-miR-138 hsa-miR-492
    hsa-miR-215 hsa-miR-135a*/mmu-miR-135a*
    hsa-miR-302a/mmu-miR-302a ebv-miR-BART20-3p
    hsa-miR-96/mmu-miR-96/rno- hsa-miR-586
    miR-96 hsa-miR-338-5p/mmu-miR-338-
    hsa-miR-218-2*/mmu-miR- 5p/rno-miR-338*
    218-2*/rno-miR-218* hsa-miR-92b*
    kshv-miR-K12-7 hiv1-miR-H1
    hsa-miR-301a/mmu-miR- hsa-miR-508-5p
    301a/rno-miR-301a hsa-miR-542-5p/mmu-miR-542-
    5p/rno-miR-542-5p
    hsa-miR-490-5p
    hsa-miR-663
    hsa-miR-433/mmu-miR-433/rno-
    miR-433
  • Finally, we identified sets of microRNAs that can distinguish between each pair of B cell malignancies in the study. Lists of those microRNAs are shown in Appendix B, Tables 16 to 30. In certain embodiments, each of the listed microRNAs is sufficient to distinguish between the two B cell malignancies listed in the table description.
  • The consistent expression of a number of miRNAs in a diverse set of B cell malignances suggests a role for miRNAs in the maintenance of tumor phenotype. Assays for stage-specific B cell markers such as BCL6, a marker for GC cells, are essential in the clinical diagnosis of B cell malignancies. Our data suggest that stage-specific biology in B cell malignancies is retained at the miRNA level. Recent work has demonstrated the utility of gene expression profiling in reliably distinguishing closely related B cell malignancies. See Hummel et al. N Engl J Med. 2006; 354:2419-2430; Dave et al. N Engl J Med. 2006; 354:2431-2442. However, clinical translation of gene expression profiling has proved to be difficult because of the need for freshly frozen tissue. Since intact miRNAs can be isolated from tissues preserved using standard methods (see, e.g., Doleshal et al. J Mol Diagn. 2008; 10:203-211; Xi et al. Rna. 2007; 13:1668-1674), diagnostic methods based upon miRNA profiles could be fairly easy to translate to clinical use.
  • Interestingly, in contrast to a previous study (Lu et al. Nature 2005; 435:834-838), we did not note a decrease in the expression of the total number or overall expression levels of miRNAs in B cell malignancies compared to normal lymph nodes. Although B cell malignancies maintain the expression of a number of stage-specific miRNAs, their miRNA expression patterns are clearly deranged compared to normal lymph nodes. The consequences of altered miRNA expression in B cell tumors would be important to explore in future studies.
  • In conclusion, our study demonstrates that mature B cell subsets have distinct patterns of microRNA expression, suggesting a role for miRNAs in B cell differentiation. We provide experimental evidence that transcription factors such as LM02 and PRDM1 are direct targets of differentially expressed miRNAs. B cell malignancies demonstrate a distinct pattern of miRNA expression that could be useful in distinguishing morphologically identical subtypes of these tumors. The conserved expression of stage-specific microRNAs in normal and malignant B cells suggests a role for microRNAs in the maintenance of the mature B cell phenotype.
  • Example 6 Differential Expression of miRNAs in ABC DLBCL Vs. GBC DLBCL Malignancies
  • As discussed above, microRNAs have shown promise as biomarkers in a number of malignancies. Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma and is known to comprise at least 2 molecularly distinct subgroups with different responses to standard therapy. These two distinct subgroups are typically identified as ABC DLBCL and GC (or GCB) DLBCL.
  • However, the current methods used to distinguish GCB from non GCB DLBCL are limited fashion and can yield inconsistent results. While gene expression profiling remains the gold standard for distinguishing these 2 molecular subgroups it is not routinely performed in clinical laboratories. In an effort to expand and improve the existing analytical options we sought to develop microRNA-based assays. We created RNA libraries from 31 different samples and performed deep sequencing analysis to identify the present miRNAs.
  • Small RNA Library Creation and Deep Sequencing
  • Total RNA was extracted from the 31 samples using the phenol-chloroform method to preserve microRNAs, using Ambion reagents. Total RNA (typically 5 μg) from each sample was run on denaturing polyacrylamide-urea gels. The ˜17-25 nucleotide RNAs were excised from the gel, ligated to sequencing adaptors on both ends and reverse transcribed. The resulting cDNA library was PCR-amplified for 15 cycles and gel purified on 6% acrylamide gel. The gel-purified amplicon quality and quantity were analyzed on a 6% acrylamide gel relative to oligonucleotides of known concentration and size. 120 μl of 1-4 μM library were loaded on to the Illumina cluster station, where DNA molecules were attached to high-density universal adaptors in the flow cells and amplified. The DNA clusters generated via this process were sequenced with sequencing-by-synthesis technology, where successive high-resolution images of the four-color fluorescence excitation dependent on the base incorporated during each cycle were captured. Sequencing reads were generated for each of the 31 samples and base calls were rendered using Illumina software. All the primary sequencing data and gene expression data is publicly available through the GEO archive through accession GSE22898.
  • The small RNA libraries from the 31 samples which were subjected to massively parallel, high-throughput sequencing using the Illumina platform generated a total of 328 million separate reads. Our approach to analyzing the sequences and discovering microRNAs broadly follows a previously described method (see, Zheng, Q., et al. GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis, Nucleic acids Res. 2008; 36 (Web Server issue: W358-363). All bioinformatics analyses were performed using a cluster of 1024 Linux computer nodes. Preprocessing was carried out using locally written Shell and Perl scripts.
  • From the raw sequences generated by high-throughput sequencing, the 3′- and 5′-adaptor sequences were trimmed. Low quality sequences were identified as those sequencing reads that contained stretches of consecutive identical bases or uncalled nucleotides (N) in the first 12 bases and sequencing reads shorter than 17 nucleotides. To minimize redundancy, reads were initially curtailed to the first 22 nucleotides and identical sequences were represented with a single fasta entry for analysis. Each unique sequence was mapped to the reference genome (Ensembl, build 50) and reads were filtered such that only perfect alignments (full length, 100% identity) were retained. Reads that aligned to more than five positions in the genome and reads that overlapped with the UCSC RNA genes were identified and excluded from microRNA analysis.
  • Identification and Analysis of the Captured miRNA Sequences
  • Sequences that occurred 20 or more times in at least one sample were consolidated and annotated for the 31 samples. Genomic loci that overlapped with microRNAs described in miRBase (version 13) were identified as known microRNAs (see Table 31). The remaining genomic loci were identified as encoding candidate novel microRNAs (see Table 32).
  • The vast majority (96%) of the candidate novel microRNAs were found in more than one sample, with only a small minority of microRNAs were expressed exclusively in a specific B cell subset or malignancy. Many of the microRNAs that we identified in normal and malignant B cells were expressed at ten-fold or higher levels in these non B cell cases. These findings suggest that the microRNAs we have identified are broadly expressed and may have roles in a number of diverse tissue types.
  • miRNA Profiling Using Real-Time PCR
  • miRNA expression profiling was conducted using the Applied Biosystems 384-well multiplexed real-time PCR assay using 400 ng of total RNA. Eight reactions, each containing 50 ng of RNA and a multiplex looped primer pool with endogenous small nucleolar (sno)-RNA controls, were used to reverse-transcribe the miRNAs in parallel fashion (see Tables 33 and 34 for primers). The completed reactions were loaded onto the 384-well plate per manufacturer's instructions, and real-time PCR was run on the ABI 7900HT Prism instrument. For each 384-well plate, we used the automatically determined cycle-threshold (CT) using the SDS 2.2.1 software (Applied Biosystems). Consistent with manufacturer recommendations, a CT greater than 35 was treated as undetected. The probes deemed to be present were normalized to the average expression of a sno-RNA control. The expression values were calculated as 2−ΔCT, then median centered to 500 and log 2-transformed.
  • For further validation of the deep sequencing results, we selected candidate novel microRNAs (see Table 34) that were detectably measured in at the sequencing data from least one of four diffuse large B cell lymphoma (DLBCL) cases. Using stem-loop reverse transcription (Ashburner, M., et al., Nat Genet. (2000); 25(1):25-29) for quantitative PCR, we tested the expression of the candidate microRNAs in 101 primary tumors from patients with DLBCL and found that about 92% were detectably measured by real-time PCR in at least 10% of these cases, suggesting that real-time PCR reproducibly identifies microRNAs that are expressed in lymphomas. We also used real-time PCR to measure the expression of known microRNAs (see Table 33) in the same 101 samples and found that over 90% of these were also detected in at least 10% of the cases using real-time PCR. We found that six of the seven RT-PCR constructs that targeted RNA hairpins that had low probability of being a microRNA resulted in no detectable signal. These results suggest that our assays have high specificity for microRNAs and that the computational predictions based on our sequencing data correctly identified microRNAs.
  • Differentiating ABC DLBCL Vs. GCB DLBCL Malignancies
  • Gene expression profiling of patients with DLBCL has demonstrated that the tumors comprise at least two distinct diseases with different response rates to standard chemotherapy regimens (Chen, C., et al., Nucleic Acids Res. (2005); 33(20):e179). We hypothesized that microRNAs might be used to make this clinically important distinction for which gene expression profiling remains the gold standard. We performed gene expression profiling on 101 DLBCL cases and further subdivided these cases into the molecular subgroups.
  • Tumor samples from 101 patients with diffuse large B cell lymphoma were obtained at the time of diagnosis and freshly frozen. These cases were profiled using Affymetrix Gene 1.0 ST arrays. The molecular subgroups were distinguished using a Bayesian approach described previously (Ambros, V., et al., RNA (2003);9(3):277-279).
  • We found that 25 microRNAs with the highest t-statistic were equally efficacious as the gene expression profiling in differentiating the two groups of DLBCL with over 95% overlap between the classifications rendered by the two methods, using leave out one cross-validation (see Table 35). Interestingly, a subset of these 25 predictor microRNAs was candidate novel microRNAs, suggesting a biological and clinical relevance for these candidate novel microRNAs in DLBCL tumors.
  • Our work provides an exhaustive identification of the microRNAs in normal and malignant B cells; that is a prerequisite to the delineation of their role. Further, we have developed a comprehensive framework that spans the identification of microRNAs from deep sequencing data to measuring their expression using real-time PCR and validating their expression in primary human tumors.
  • It is also conceivable that some of the low-abundance microRNAs that we have identified in our study may be expressed at higher levels in other development stages or in other cell types. This notion is confirmed by our examination of the novel microRNAs in non B cell data. For instance, a number of the microRNAs that we discovered were also present at 10-fold or higher levels in cell lines derived from breast cancer and cervical cancer, suggesting that the microRNAs that we have discovered in B cells have broad biological significance.
  • Deep Sequencing Reveals a Novel miRNA Cluster that Regulates the TGF-β Pathway
  • Although microRNAs appear to be distributed throughout the genome, a number of microRNAs have been found in clusters such as miR-17-92 that are transcribed from a single primary transcript and cleaved into the individual microRNAs by the enzyme DROSHA. We found 2 separate clusters of candidate novel microRNAs on chromosome 9 and chromosome 14 (within the IgH locus), respectively. The first cluster was previously annotated as a hypothetical gene LOC100130622, and subsequently discarded from Refseq when no associated protein was identified. Our data demonstrate that this cluster (miR-2355), conserved only in primates, encodes 6 separate microRNAs: has-miR-2355a-1, has-miR-2356-1, has-miR-2355a-2, has-miR-2356-2, hsa-miR2355a-3, and hsa-miR-2355b (see Table 32 for sequence).
  • In order to evaluate whether the microRNAs encoded in these clusters originate from the same primary transcript, we took KMS12 multiple myeloma cells which express these microRNAs and used siRNA to knock-down the expression of the microRNA processing enzyme Drosha. This enzyme acts at the first step of microRNA processing by cleaving microRNA precursors from the primary transcript. We found that decreased Drosha expression was associated with increased accumulation of primary transcripts of both the miR-17-92 cluster as well as the novel miR-2355 cluster. MicroRNAs from miR-2355 cluster were found to be expressed more highly in normal germinal center (GC) B cells compared to memory cells.
  • The microRNAs of this cluster all share the same seed sequence, suggesting that they target the same genes. Among the computationally predicted targets of this microRNA cluster, we identified SMAD2 and SMAD3 which are well known mediators of the TGF-beta signaling pathway. We noted that gene expression of both SMAD2 and SMAD3 in our set of 101 DLBCLs were inversely correlated with this cluster (P<0.001, correlation test). Gene set enrichment analysis revealed that expression of the TGF-beta pathway in DLBCL samples varied inversely with the expression of the microRNA cluster, with a higher expression of the microRNA associated with a lower expression of the pathway (P<10−6), which has been noted as a factor in the biology of these tumors.
  • TABLE 31
    miRNAs identified by deep sequencing analysis.
    Putative
    Mature/ miRBase miRBase
    SEQ Minor Mature/ Mature/Minor miRBase SEQ
    ID Mature Sequence miRNA  miRBase Minor Accession Mature/Minor ID
    NO. Captured ID ID ID Number Sequence NO.
      1 CUGCGCAAGCUACUGCCUUGCU hsa-let- hsa-let- hsa-let- MIMAT0004585 CUGCGCAAGCUACUGCCUUGCU  393
    7i* 7i 7i*
      2 CCACGGAUGUUUGAGCAUGUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0004516 ACGGAUGUUUGAGCAUGUGCUA  394
    105-1* 105-1 105*
      3 CCACGGAUGUUUGAGCAUGUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0004516 ACGGAUGUUUGAGCAUGUGCUA  395
    105-2* 105-2 105*
      4 UACUGCAAUGUAAGCACUUCUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004517 CUGCAAUGUAAGCACUUCUUAC  396
    106a* 106a 106a*
      5 CAUUAUUACUUUUGGUACGCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000444 CAUUAUUACUUUUGGUACGCG  397
    126* 126 126*
      6 AAGCCCUUACCCCAAAAAGUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0004548 AAGCCCUUACCCCAAAAAGUAU  398
    129* 129-1 129*
      7 AAGCCCUUACCCCAAAAAGCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0004605 AAGCCCUUACCCCAAAAAGCAU  399
    129-2* 129-2 129-3p
      8 UCUACAGUGCACGUGUCUCCAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000250 UCUACAGUGCACGUGUCUCCAG  400
    139-5p 139 139-5p
      9 CUGGUACAGGCCUGGGGGACAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004610 CUGGUACAGGCCUGGGGGACAG  401
    150* 150 150*
     10 ACUGCAGUGAAGGCACUUGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000071 ACUGCAGUGAAGGCACUUGUAG  402
    17* 17 17*
     11 UGAAUUACCGAAGGGCCAUAA hsa-mir- hsa-mir- hsa-miR- MIMAT0004560 GUGAAUUACCGAAGGGCCAUAA  403
    183* 183 183*
     12 AGGGGCUGGCUUUCCUCUGGUC hsa-mir- hsa-mir- hsa-miR- MIMAT0004611 AGGGGCUGGCUUUCCUCUGGUC  404
    185* 185 185*
     13 ACUGCCCUAAGUGCUCCUUCUGG hsa-mir- hsa-mir- hsa-miR- MIMAT0002891 ACUGCCCUAAGUGCUCCUUCUGG  405
    18a* 18a 18a*
     14 AACUGGCCUACAAAGUCCCAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000459 AACUGGCCUACAAAGUCCCAGU  406
    193a-3p 193a 193a-3p
     15 CGGGGUUUUGAGGGCGAGAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004767 CGGGGUUUUGAGGGCGAGAUGA  407
    193b* 193b 193b*
     16 CCCAGUGUUCAGACUACCUGUUC hsa-mir- hsa-mir- hsa-miR- MIMAT0000231 CCCAGUGUUCAGACUACCUGUUC  408
    199a-2* 199a-2 199a-5p
     17 UAGUUUUGCAUAGUUGCACUAC hsa-mir- hsa-mir- hsa-miR- MIMAT0004490 AGUUUUGCAUAGUUGCACUACA  409
    19a* 19a 19a*
     18 AGUUUUGCAGGUUUGCAUCCAGC hsa-mir- hsa-mir- hsa-miR- MIMAT0004491 AGUUUUGCAGGUUUGCAUCCAGC  410
    19b-1* 19b-1 19b-1*
     19 ACUGUAGUAUGGGCACUUCCAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004752 ACUGUAGUAUGGGCACUUCCAG  411
    20b* 20b 20b*
     20 ACCUGGCAUACAAUGUAGAUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004568 ACCUGGCAUACAAUGUAGAUUU  412
    221* 221 221*
     21 GGGUUCCUGGCAUGCUGAUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004587 UGGGUUCCUGGCAUGCUGAUUU  413
    23b* 23b 23b*
     22 AGGCGGAGACUUGGGCAAUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0004498 AGGCGGAGACUUGGGCAAUUG  414
    25* 25 25*
     23 AGAGCUUAGCUGAUUGGUGAAC hsa-mir- hsa-mir- hsa-miR- MIMAT0004588 AGAGCUUAGCUGAUUGGUGAAC  415
    27b* 27b 27b*
     24 CUGGGAGGUGGAUGUUUACUUC hsa-mir- hsa-mir- hsa-miR- MIMAT0004589 CUGGGAGGUGGAUGUUUACUUC  416
    30b* 30b 30b*
     25 CUGGGAGAGGGUUGUUUACUCC hsa-mir- hsa-mir- hsa-miR- MIMAT0004674 CUGGGAGAGGGUUGUUUACUCC  417
    30c-1* 30c-1 30c-1*
     26 CUGGGAGAAGGCUGUUUACUCU hsa-mir- hsa-mir- hsa-miR- MIMAT0004550 CUGGGAGAAGGCUGUUUACUCU  418
    30c-2* 30c-2 30c-2*
     27 CUUUCAGUCGGAUGUUUACAGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000693 CUUUCAGUCGGAUGUUUACAGC  419
    30e* 30e 30e*
     28 UCCCUGUCCUCCAGGAGCUCACG hsa-mir- hsa-mir- hsa-miR- MIMAT0000764 UCCCUGUCCUCCAGGAGCUCACG  420
    339-5p 339 339-5p
     29 UCUCACACAGAAAUCGCACCCGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000753 UCUCACACAGAAAUCGCACCCGU  421
    342-3p 342 342-3p
     30 AAUCAGCAAGUAUACUGCCCUA hsa-mir- hsa-mir- hsa-miR- MIMAT0004557 CAAUCAGCAAGUAUACUGCCCU  422
    34a* 34a 34a*
     31 UCCCCCAGGUGUGAUUCUGAUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004682 UCCCCCAGGUGUGAUUCUGAUUU  423
    361-3p 361 361-3p
     32 AAUCCUUGGAACCUAGGUGUGAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000705 AAUCCUUGGAACCUAGGUGUGAGU  424
    362-5p 362 362-5p
     33 AGGGACUUUCAGGGGCAGCUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0009199 AGGGACUUUCAGGGGCAGCUGU  425
    365-2* 365-2 365*
     34 CUUAUCAGAUUGUAUUGUAAUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004688 CUUAUCAGAUUGUAUUGUAAUU  426
    374a* 374a 374a*
     35 CUUAGCAGGUUGUAUUAUCAUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004956 CUUAGCAGGUUGUAUUAUCAUU  427
    374b* 374b 374b*
     36 AGGUUACCCGAGCAACUUUGCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0001638 AGGUUACCCGAGCAACUUUGCAU  428
    409-5p 409 409-5p
     37 CAAAACGUGAGGCGCUGCUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0004749 CAAAACGUGAGGCGCUGCUAU  429
    424* 424 424*
     38 UAUGUGCCUUUGGACUACAUCG hsa-mir- hsa-mir- hsa-miR- MIMAT0003150 UAUGUGCCUUUGGACUACAUCG  430
    455-5p 455 455-5p
     39 GUCAUACACGGCUCUCCUCUCU hsa-mir- hsa-mir- hsa-miR- MIMAT0002176 GUCAUACACGGCUCUCCUCUCU  431
    485-3p 485 485-3p
     40 UGUCUUACUCCCUCAGGCACAU hsa-mir- hsa-mir- hsa-miR- MIMAT0003257 UGUCUUACUCCCUCAGGCACAU  432
    550-1* 550-1 550*
     41 UGUCUUACUCCCUCAGGCACAU hsa-mir- hsa-mir- hsa-miR- MIMAT0003257 UGUCUUACUCCCUCAGGCACAU  433
    550-2* 550-2 550*
     42 GAAAUCAAGCGUGGGUGAGACC hsa-mir- hsa-mir- hsa-miR- MIMAT0004794 GAAAUCAAGCGUGGGUGAGACC  434
    551b* 551b 551b*
     43 AUUCUAAUUUCUCCACGUCUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0003241 AUUCUAAUUUCUCCACGUCUUU  435
    576-5p 576 576-5p
     44 UCAGAACAAAUGCCGGUUCCCAGA hsa-mir- hsa-mir- hsa-miR- MIMAT0003256 UCAGAACAAAUGCCGGUUCCCAGA  436
    589* 589 589*
     45 GAGCUUAUUCAUAAAAGUGCAG hsa-mir- hsa-mir- hsa-miR- MIMAT0003258 GAGCUUAUUCAUAAAAGUGCAG  437
    590-5p 590 590-5p
     46 GGGGGUCCCCGGUGCUCGGAUC hsa-mir- hsa-mir- hsa-miR- MIMAT0004804 GGGGGUCCCCGGUGCUCGGAUC  438
    615-5p 615 615-5p
     47 GACUAUAGAACUUUCCCCCUCA hsa-mir- hsa-mir- hsa-miR- MIMAT0004808 GACUAUAGAACUUUCCCCCUCA  439
    625* 625 625*
     48 UGGUGGGCCGCAGAACAUGUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003330 UGGUGGGCCGCAGAACAUGUGC  440
    654-5p 654 654-5p
     49 AGGAAGCCCUGGAGGGGCUGGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0003880 AGGAAGCCCUGGAGGGGCUGGAG  441
    671-5p 671 671-5p
     50 AACUAGACUGUGAGCUUCUAGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004927 CAACUAGACUGUGAGCUUCUAG  442
    708* 708 708*
     51 CAACAAAUCACAGUCUGCCAUA hsa-mir- hsa-mir- hsa-miR- MIMAT0004553 CAACAAAUCACAGUCUGCCAUA  443
    7-1* 7-1 7-1*
     52 AUAAAGCUAGAUAACCGAAAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000442 AUAAAGCUAGAUAACCGAAAGU  444
    9-1* 9-1 9*
     53 AUAAAGCUAGAUAACCGAAAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000442 AUAAAGCUAGAUAACCGAAAGU  445
    9-2* 9-2 9*
     54 AGGGACGGGACGCGGUGCAGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0004792 AGGGACGGGACGCGGUGCAGUG  446
    92b* 92b 92b*
     55 AUAAAGCUAGAUAACCGAAAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000442 AUAAAGCUAGAUAACCGAAAGU  447
    9-3* 9-3 9*
     56 UGAGGUAGUAGGUUGUAUAGUU hsa-let- hsa-let- hsa-let- MIMAT0000062 UGAGGUAGUAGGUUGUAUAGUU  448
    7a-2 7a-2 7a
     57 UGAGGUAGUAGGUUGUAUAGUU hsa-let- hsa-let- hsa-let- MIMAT0000062 UGAGGUAGUAGGUUGUAUAGUU  449
    7a-3 7a-3 7a
     58 UGAGGUAGUAGGUUGUAUGGUU hsa-let- hsa-let- hsa-let- MIMAT0000064 UGAGGUAGUAGGUUGUAUGGUU  450
    7c 7c 7c
     59 UGAGGUAGGAGGUUGUAUAGUU hsa-let- hsa-let- hsa-let- MIMAT0000066 UGAGGUAGGAGGUUGUAUAGUU  451
    7e 7e 7e
     60 UGAGGUAGUAGAUUGUAUAGUU hsa-let- hsa-let- hsa-let- MIMAT0000067 UGAGGUAGUAGAUUGUAUAGUU  452
    7f-1 7f-1 7f
     61 UGAGGUAGUAGUUUGUACAGUU hsa-let- hsa-let- hsa-let- MIMAT0000414 UGAGGUAGUAGUUUGUACAGUU  453
    7g 7g 7g
     62 UGAGGUAGUAGUUUGUGCUGUU hsa-let- hsa-let- hsa-let- MIMAT0000415 UGAGGUAGUAGUUUGUGCUGUU  454
    7i 7i 7i
     63 AACCCGUAGAUCCGAACUUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000098 AACCCGUAGAUCCGAACUUGUG  455
    100 100 100
     64 UACAGUACUGUGAUAACUGAA hsa-mir- hsa-mir- hsa-miR- MIMAT0000099 UACAGUACUGUGAUAACUGAA  456
    101-1 101-1 101
     65 GUACAGUACUGUGAUAACUGAA hsa-mir- hsa-mir- hsa-miR- MIMAT0000099 UACAGUACUGUGAUAACUGAA  457
    101-2 101-2 101
     66 AGCAGCAUUGUACAGGGCUAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000101 AGCAGCAUUGUACAGGGCUAUGA  458
    103-1 103-1 103
     67 AGCAGCAUUGUACAGGGCUAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000101 AGCAGCAUUGUACAGGGCUAUGA 4589
    103-2 103-2 103
     68 AAAUGCUCAGACUCCUGUGGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000102 UCAAAUGCUCAGACUCCUGUGGU  460
    105-1 105-1 105
     69 AAAUGCUCAGACUCCUGUGGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000102 UCAAAUGCUCAGACUCCUGUGGU  461
    105-2 105-2 105
     70 AAAAGUGCUUACAGUGCAGGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000103 AAAAGUGCUUACAGUGCAGGUAG  462
    106a 106a 106a
     71 UAAAGUGCUGACAGUGCAGAU hsa-mir- hsa-mir- hsa-miR- MIMAT0000680 UAAAGUGCUGACAGUGCAGAU  463
    106b 106b 106b
     72 AGCAGCAUUGUACAGGGCUAUCA hsa-mir- hsa-mir- hsa-miR- MIMAT0000104 AGCAGCAUUGUACAGGGCUAUCA  464
    107 107 107
     73 UACCCUGUAGAUCCGAAUUUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000253 UACCCUGUAGAUCCGAAUUUGUG  465
    10a 10a 10a
     74 UACCCUGUAGAACCGAAUUUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000254 UACCCUGUAGAACCGAAUUUGUG  466
    10b 10b 10b
     75 UGGAAUGUAAAGAAGUAUGUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0000416 UGGAAUGUAAAGAAGUAUGUAU  467
    1-1 1-1 1
     76 UGGAAUGUAAAGAAGUAUGUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0000416 UGGAAUGUAAAGAAGUAUGUAU  468
    1-2 1-2 1
     77 UGGAGUGUGACAAUGGUGUUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000421 UGGAGUGUGACAAUGGUGUUUG  469
    122 122 122
     78 UAAGGCACGCGGUGAAUGCC hsa-mir- hsa-mir- hsa-miR- MIMAT0000422 UAAGGCACGCGGUGAAUGCC  470
    124-1 124-1 124
     79 UAAGGCACGCGGUGAAUGCC hsa-mir- hsa-mir- hsa-miR- MIMAT0000422 UAAGGCACGCGGUGAAUGCC  471
    124-2 124-2 124
     80 UAAGGCACGCGGUGAAUGCC hsa-mir- hsa-mir- hsa-miR- MIMAT0000422 UAAGGCACGCGGUGAAUGCC  472
    124-3 124-3 124
     81 ACCCGUCCCGUUCGUCCCCGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0005899 ACCCGUCCCGUUCGUCCCCGGA  473
    1247 1247 1247
     82 ACGGUGCUGGAUGUGGCCUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0005902 ACGGUGCUGGAUGUGGCCUUU  474
    1250 1250 1250
     83 AGAAGGAAAUUGAAUUCAUUUA hsa-mir- hsa-mir- hsa-miR- MIMAT0005944 AGAAGGAAAUUGAAUUCAUUUA  475
    1252 1252 1252
     84 AGCCUGGAAGCUGGAGCCUGCAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0005905 AGCCUGGAAGCUGGAGCCUGCAGU  476
    1254 1254 1254
     85 AGGAUGAGCAAAGAAAGUAGAUU hsa-mir- hsa-mir- hsa-miR- MIMAT0005906 AGGAUGAGCAAAGAAAGUAGAUU  477
    1255a 1255a 1255a
     86 AGGCAUUGACUUCUCACUAGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0005907 AGGCAUUGACUUCUCACUAGCU  478
    1256 1256 1256
     87 CGUACCGUGAGUAAUAAUGCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000445 UCGUACCGUGAGUAAUAAUGCG  479
    126 126 126
     88 AUGGGUGAAUUUGUAGAAGGAU hsa-mir- hsa-mir- hsa-miR- MIMAT0005914 AUGGGUGAAUUUGUAGAAGGAU  480
    1262 1262 1262
     89 AUGGUACCCUGGCAUACUGAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0005915 AUGGUACCCUGGCAUACUGAGU  481
    1263 1263 1263
     90 CAGGAUGUGGUCAAGUGUUGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0005918 CAGGAUGUGGUCAAGUGUUGUU  482
    1265 1265 1265
     91 CCUCAGGGCUGUAGAACAGGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0005920 CCUCAGGGCUGUAGAACAGGGCU  483
    1266 1266 1266
     92 CUGGACUGAGCCGUGCUACUGG hsa-mir- hsa-mir- hsa-miR- MIMAT0005923 CUGGACUGAGCCGUGCUACUGG  484
    1269 1269 1269
     93 CUGGAGAUAUGGAAGAGCUGUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0005924 CUGGAGAUAUGGAAGAGCUGUGU  485
    1270 1270 1270
     94 CUUGGCACCUAGCAAGCACUCA hsa-mir- hsa-mir- hsa-miR- MIMAT0005796 CUUGGCACCUAGCAAGCACUCA  486
    1271 1271 1271
     95 UCGGAUCCGUCUGAGCUUGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000446 UCGGAUCCGUCUGAGCUUGGCU  487
    127-3p 127 127-3p
     96 UACGUAGAUAUAUAUGUAUUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0005933 UACGUAGAUAUAUAUGUAUUUU  488
    1277 1277 1277
     97 UAGUACUGUGCAUAUCAUCUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0005936 UAGUACUGUGCAUAUCAUCUAU  489
    1278 1278 1278
     98 UCACAGUGAACCGGUCUCUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000424 UCACAGUGAACCGGUCUCUUU  490
    128-1 128-1 128
     99 UCACAGUGAACCGGUCUCUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000424 UCACAGUGAACCGGUCUCUUU  491
    128-2 128-2 128
    100 CUUUUUGCGGUCUGGGCUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000242 CUUUUUGCGGUCUGGGCUUGC  492
    129-1 129-1 129-5p
    101 CUUUUUGCGGUCUGGGCUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000242 CUUUUUGCGGUCUGGGCUUGC  493
    129-2 129-2 129-5p
    102 UGUGAGGUUGGCAUUGUUGUCU hsa-mir- hsa-mir- hsa-miR- MIMAT0005884 UGUGAGGUUGGCAUUGUUGUCU  494
    1294 1294 1294
    103 UUAGGCCGCAGAUCUGGGUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0005885 UUAGGCCGCAGAUCUGGGUGA  495
    1295 1295 1295
    104 UUCAUUCGGCUGUCCAGAUGUA hsa-mir- hsa-mir- hsa-miR- MIMAT0005800 UUCAUUCGGCUGUCCAGAUGUA  496
    1298 1298 1298
    105 UUGCAGCUGCCUGGGAGUGACUUC hsa-mir- hsa-mir- hsa-miR- MIMAT0005797 UUGCAGCUGCCUGGGAGUGACUUC  497
    1301 1301 1301
    106 CGGUUUGAGGCUACAGUGAGAU hsa-mir- hsa-mir- hsa-miR- MIMAT0005892 UUUGAGGCUACAGUGAGAUGUG  498
    1304 1304 1304
    107 ACGUUGGCUCUGGUGGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0005950 ACGUUGGCUCUGGUGGUG  499
    1306 1306 1306
    108 ACUCGGCGUGGCGUCGGUCGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0005951 ACUCGGCGUGGCGUCGGUCGUG  500
    1307 1307 1307
    109 CAGUGCAAUGUUAAAAGGGCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0000425 CAGUGCAAUGUUAAAAGGGCAU  501
    130a 130a 130a
    110 CAGUGCAAUGAUGAAAGGGCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0000691 CAGUGCAAUGAUGAAAGGGCAU  502
    130b 130b 130b
    111 UAACAGUCUACAGCCAUGGUCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000426 UAACAGUCUACAGCCAUGGUCG  503
    132 132 132
    112 ACCGUGGCUUUCGAUUGUUACU hsa-mir- hsa-mir- hsa-miR- MIMAT0004594 ACCGUGGCUUUCGAUUGUUACU  504
    132* 132 132*
    113 UGUGACUGGUUGACCAGAGGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000447 UGUGACUGGUUGACCAGAGGGG  505
    134 134 134
    114 UAUGGCUUUUCAUUCCUAUGUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000758 UAUGGCUUUUCAUUCCUAUGUGA  506
    135b 135b 135b
    115 ACUCCAUUUGUUUUGAUGAUGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000448 ACUCCAUUUGUUUUGAUGAUGGA  507
    136 136 136
    116 AGCUGGUGUUGUGAAUCAGGCCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000430 AGCUGGUGUUGUGAAUCAGGCCG  508
    138-1 138-1 138
    117 AGCUGGUGUUGUGAAUCAGGCCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000430 AGCUGGUGUUGUGAAUCAGGCCG  509
    138-2 138-2 138
    118 UGGAGACGCGGCCCUGUUGGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004552 GGAGACGCGGCCCUGUUGGAGU  510
    139-3p 139 139-3p
    119 UACCACAGGGUAGAACCACGG hsa-mir- hsa-mir- hsa-miR- MIMAT0004597 UACCACAGGGUAGAACCACGG  511
    140-3p 140 140-3p
    120 UAACACUGUCUGGUAAAGAUGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000432 UAACACUGUCUGGUAAAGAUGG  512
    141 141 141
    121 CCCAUAAAGUAGAAAGCACU hsa-mir- hsa-mir- hsa-miR- MIMAT0000433 CAUAAAGUAGAAAGCACUACU  513
    142 142 142-5p
    122 UGAGAUGAAGCACUGUAGCUC hsa-mir- hsa-mir- hsa-miR- MIMAT0000435 UGAGAUGAAGCACUGUAGCUC  514
    143 143 143
    123 GGAUAUCAUCAUAUACUGUAAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004600 GGAUAUCAUCAUAUACUGUAAG  515
    144 144 144*
    124 GUCCAGUUUUCCCAGGAAUCCCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000437 GUCCAGUUUUCCCAGGAAUCCCU  516
    145 145 145
    125 UGAGAACUGAAUUCCAUGGGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000449 UGAGAACUGAAUUCCAUGGGUU  517
    146a 146a 146a
    126 UGAGAACUGAAUUCCAUAGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0002809 UGAGAACUGAAUUCCAUAGGCU  518
    146b 146b 146b-5p
    127 UCAGUGCACUACAGAACUUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000243 UCAGUGCACUACAGAACUUUGU  519
    148a 148a 148a
    128 UCAGUGCAUCACAGAACUUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000759 UCAGUGCAUCACAGAACUUUGU  520
    148b 148b 148b
    129 UCUCCCAACCCUUGUACCAGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000451 UCUCCCAACCCUUGUACCAGUG  521
    150 150 150
    130 CUAGACUGAAGCUCCUUGAGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000757 CUAGACUGAAGCUCCUUGAGG  522
    151-3p 151 151-3p
    131 UCAGUGCAUGACAGAACUUGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000438 UCAGUGCAUGACAGAACUUGG  523
    152 152 152
    132 UUAAUGCUAAUCGUGAUAGGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000646 UUAAUGCUAAUCGUGAUAGGGGU  524
    155 155 155
    133 UAGCAGCACAUAAUGGUUUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000068 UAGCAGCACAUAAUGGUUUGUG  525
    15a 15a 15a
    134 UAGCAGCACAUCAUGGUUUACA hsa-mir- hsa-mir- hsa-miR- MIMAT0000417 UAGCAGCACAUCAUGGUUUACA  526
    15b 15b 15b
    135 UAGCAGCACGUAAAUAUUGGCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000069 UAGCAGCACGUAAAUAUUGGCG  527
    16-1 16-1 16
    136 UAGCAGCACGUAAAUAUUGGCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000069 UAGCAGCACGUAAAUAUUGGCG  528
    16-2 16-2 16
    137 CAAAGUGCUUACAGUGCAGGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000070 CAAAGUGCUUACAGUGCAGGUAG  529
    17 17 17
    138 AACAUUCAACGCUGUCGGUGAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000256 AACAUUCAACGCUGUCGGUGAGU  530
    181a-1 181a-1 181a
    139 AACAUUCAACGCUGUCGGUGAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000256 AACAUUCAACGCUGUCGGUGAGU  531
    181a-2 181a-2 181a
    140 AACAUUCAUUGCUGUCGGUGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000257 AACAUUCAUUGCUGUCGGUGGGU  532
    181b-1 181b-1 181b
    141 AACAUUCAUUGCUGUCGGUGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000257 AACAUUCAUUGCUGUCGGUGGGU  533
    181b-2 181b-2 181b
    142 AACAUUCAACCUGUCGGUGAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000258 AACAUUCAACCUGUCGGUGAGU  534
    181c 181c 181c
    143 AACAUUCAUUGUUGUCGGUGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0002821 AACAUUCAUUGUUGUCGGUGGGU  535
    181d 181d 181d
    144 UUUGGCAAUGGUAGAACUCACACU hsa-mir- hsa-mir- hsa-miR- MIMAT0000259 UUUGGCAAUGGUAGAACUCACACU  536
    182 182 182
    145 UAUGGCACUGGUAGAAUUCACU hsa-mir- hsa-mir- hsa-miR- MIMAT0000261 UAUGGCACUGGUAGAAUUCACU  537
    183 183 183
    146 UGGACGGAGAACUGAUAAGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000454 UGGACGGAGAACUGAUAAGGGU  538
    184 184 184
    147 UGGAGAGAAAGGCAGUUCCUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000455 UGGAGAGAAAGGCAGUUCCUGA  539
    185 185 185
    148 CAAAGAAUUCUCCUUUUGGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000456 CAAAGAAUUCUCCUUUUGGGCU  540
    186 186 186
    149 CAUCCCUUGCAUGGUGGAGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000457 CAUCCCUUGCAUGGUGGAGGG  541
    188-5p 188 188-5p
    150 UAAGGUGCAUCUAGUGCAGAUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000072 UAAGGUGCAUCUAGUGCAGAUAG  542
    18a 18a 18a
    151 CAACGGAAUCCCAAAAGCAGCUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000440 CAACGGAAUCCCAAAAGCAGCUG  543
    191 191 191
    152 CUGACCUAUGAAUUGACAGCC hsa-mir- hsa-mir- hsa-miR- MIMAT0000222 CUGACCUAUGAAUUGACAGCC  544
    192 192 192
    153 UGGGUCUUUGCGGGCGAGAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004614 UGGGUCUUUGCGGGCGAGAUGA  545
    193a-5p 193a 193a-5p
    154 AACUGGCCCUCAAAGUCCCGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0002819 AACUGGCCCUCAAAGUCCCGCU  546
    193b 193b 193b
    155 UGUAACAGCAACUCCAUGUGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000460 UGUAACAGCAACUCCAUGUGGA  547
    194-1 194-1 194
    156 UAGCAGCACAGAAAUAUUGGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000461 UAGCAGCACAGAAAUAUUGGC  548
    195 195 195
    157 UAGGUAGUUUCAUGUUGUUGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000226 UAGGUAGUUUCAUGUUGUUGGG  549
    196a-1 196a-1 196a
    158 UAGGUAGUUUCAUGUUGUUGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000226 UAGGUAGUUUCAUGUUGUUGGG  550
    196a-2 196a-2 196a
    159 UAGGUAGUUUCCUGUUGUUGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0001080 UAGGUAGUUUCCUGUUGUUGGG  551
    196b 196b 196b
    160 UUCACCACCUUCUCCACCCAGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000227 UUCACCACCUUCUCCACCCAGC  552
    197 197 197
    161 ACAGUAGUCUGCACAUUGGUUA hsa-mir- hsa-mir- hsa-miR- MIMAT0000232 ACAGUAGUCUGCACAUUGGUUA  553
    199a-1 199a-1 199a-3p
    162 ACAGUAGUCUGCACAUUGGUUA hsa-mir- hsa-mir- hsa-miR- MIMAT0000232 ACAGUAGUCUGCACAUUGGUUA  554
    199a-2 199a-2 199a-3p
    163 ACAGUAGUCUGCACAUUGGUUA hsa-mir- hsa-mir- hsa-miR- MIMAT0004563 ACAGUAGUCUGCACAUUGGUUA  555
    199b 199b 199b-3p
    164 UGUGCAAAUCUAUGCAAAACUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000073 UGUGCAAAUCUAUGCAAAACUGA  556
    19a 19a 19a
    165 UGUGCAAAUCCAUGCAAAACUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000074 UGUGCAAAUCCAUGCAAAACUGA  557
    19b-1 19b-1 19b
    166 UGUGCAAAUCCAUGCAAAACUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000074 UGUGCAAAUCCAUGCAAAACUGA  558
    19b-2 19b-2 19b
    167 UAACACUGUCUGGUAACGAUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000682 UAACACUGUCUGGUAACGAUGU  559
    200a 200a 200a
    168 UAAUACUGCCUGGUAAUGAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000318 UAAUACUGCCUGGUAAUGAUGA  560
    200b 200b 200b
    169 UAAUACUGCCGGGUAAUGAUGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000617 UAAUACUGCCGGGUAAUGAUGGA  561
    200c 200c 200c
    170 UUCCUAUGCAUAUACUUCUUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0002810 UUCCUAUGCAUAUACUUCUUUG  562
    202* 202 202*
    171 GUGAAAUGUUUAGGACCACUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000264 GUGAAAUGUUUAGGACCACUAG  563
    203 203 203
    172 UUCCCUUUGUCAUCCUAUGCCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000265 UUCCCUUUGUCAUCCUAUGCCU  564
    204 204 204
    173 UCCUUCAUUCCACCGGAGUCUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000266 UCCUUCAUUCCACCGGAGUCUG  565
    205 205 205
    174 UGGAAUGUAAGGAAGUGUGUGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000462 UGGAAUGUAAGGAAGUGUGUGG  566
    206 206 206
    175 UAAAGUGCUUAUAGUGCAGGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000075 UAAAGUGCUUAUAGUGCAGGUAG  567
    20a 20a 20a
    176 CAAAGUGCUCAUAGUGCAGGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0001413 CAAAGUGCUCAUAGUGCAGGUAG  568
    20b 20b 20b
    177 UAGCUUAUCAGACUGAUGUUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000076 UAGCUUAUCAGACUGAUGUUGA  569
    21 21 21
    178 CUGUGCGUGUGACAGCGGCUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000267 CUGUGCGUGUGACAGCGGCUGA  570
    210 210 210
    179 UAACAGUCUCCAGUCACGGCC hsa-mir- hsa-mir- hsa-miR- MIMAT0000269 UAACAGUCUCCAGUCACGGCC  571
    212 212 212
    180 ACAGCAGGCACAGACAGGCAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000271 ACAGCAGGCACAGACAGGCAGU  572
    214 214 214
    181 UGACCUAUGAAUUGACAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000272 AUGACCUAUGAAUUGACAGAC  573
    215 215 215
    182 AAAUCUCUGCAGGCAAAUGUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004959 AAAUCUCUGCAGGCAAAUGUGA  574
    216b 216b 216b
    183 AUACUGCAUCAGGAACUGAUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000274 UACUGCAUCAGGAACUGAUUGGA  575
    217 217 217
    184 AGAGUUGAGUCUGGACGUCCCG hsa-mir- hsa-mir- hsa-miR- MIMAT0004567 AGAGUUGAGUCUGGACGUCCCG  576
    219-1 219-1 219-1-3p
    185 AAGCUGCCAGUUGAAGAACUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000077 AAGCUGCCAGUUGAAGAACUGU  577
    22 22 22
    186 AGCUACAUUGUCUGCUGGGUUUC hsa-mir- hsa-mir- hsa-miR- MIMAT0000278 AGCUACAUUGUCUGCUGGGUUUC  578
    221 221 221
    187 AGCUACAUCUGGCUACUGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000279 AGCUACAUCUGGCUACUGGGU  579
    222 222 222
    188 CGUGUAUUUGACAAGCUGAGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004570 CGUGUAUUUGACAAGCUGAGUU  580
    223* 223 223*
    189 CAAGUCACUAGUGGUUCCGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000281 CAAGUCACUAGUGGUUCCGUU  581
    224 224 224
    190 AUCACAUUGCCAGGGAUUUCC hsa-mir- hsa-mir- hsa-miR- MIMAT0000078 AUCACAUUGCCAGGGAUUUCC  582
    23a 23a 23a
    191 AUCACAUUGCCAGGGAUUACC hsa-mir- hsa-mir- hsa-miR- MIMAT0000418 AUCACAUUGCCAGGGAUUACC  583
    23b 23b 23b
    192 UGGCUCAGUUCAGCAGGAACAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000080 UGGCUCAGUUCAGCAGGAACAG  584
    24-1 24-1 24
    193 UGGCUCAGUUCAGCAGGAACAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000080 UGGCUCAGUUCAGCAGGAACAG  585
    24-2 24-2 24
    194 CAUUGCACUUGUCUCGGUCUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000081 CAUUGCACUUGUCUCGGUCUGA  586
    25 25 25
    195 UUCAAGUAAUCCAGGAUAGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000082 UUCAAGUAAUCCAGGAUAGGCU  587
    26a-1 26a-1 26a
    196 UUCAAGUAAUCCAGGAUAGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000082 UUCAAGUAAUCCAGGAUAGGCU  588
    26a-2 26a-2 26a
    197 UUCAAGUAAUUCAGGAUAGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000083 UUCAAGUAAUUCAGGAUAGGU  589
    26b 26b 26b
    198 UUCACAGUGGCUAAGUUCCGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000084 UUCACAGUGGCUAAGUUCCGC  590
    27a 27a 27a
    199 UUCACAGUGGCUAAGUUCUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000419 UUCACAGUGGCUAAGUUCUGC  591
    27b 27b 27b
    200 CACUAGAUUGUGAGCUCCUGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004502 CACUAGAUUGUGAGCUCCUGGA  592
    28 28 28-3p
    201 GAGGGUUGGGUGGAGGCUCUCC hsa-mir- hsa-mir- hsa-miR- MIMAT0004679 GAGGGUUGGGUGGAGGCUCUCC  593
    296-3p 296 296-3p
    202 AUGGUUUACCGUCCCACAUACA hsa-mir- hsa-mir- hsa-miR- MIMAT0002890 UGGUUUACCGUCCCACAUACAU  594
    299-5p 299 299-5p
    203 UAGCACCAUCUGAAAUCGGUUA hsa-mir- hsa-mir- hsa-miR- MIMAT0000086 UAGCACCAUCUGAAAUCGGUUA  595
    29a 29a 29a
    204 UAGCACCAUUUGAAAUCAGUGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000100 UAGCACCAUUUGAAAUCAGUGUU  596
    29b-1 29b-1 29b
    205 UAGCACCAUUUGAAAUCAGUGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000100 UAGCACCAUUUGAAAUCAGUGUU  597
    29b-2 29b-2 29b
    206 UAGCACCAUUUGAAAUCGGUUA hsa-mir- hsa-mir- hsa-miR- MIMAT0000681 UAGCACCAUUUGAAAUCGGUUA  598
    29c 29c 29c
    207 CAGUGCAAUGAUAUUGUCAAAGC hsa-mir- hsa-mir- hsa-miR- MIMAT0004958 CAGUGCAAUGAUAUUGUCAAAGC  599
    301b 301b 301b
    208 UGUAAACAUCCUCGACUGGAAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000087 UGUAAACAUCCUCGACUGGAAG  600
    30a 30a 30a
    209 UGUAAACAUCCUACACUCAGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000420 UGUAAACAUCCUACACUCAGCU  601
    30b 30b 30b
    210 UGUAAACAUCCUACACUCUCAGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000244 UGUAAACAUCCUACACUCUCAGC  602
    30c-1 30c-1 30c
    211 UGUAAACAUCCUACACUCUCAGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000244 UGUAAACAUCCUACACUCUCAGC  603
    30c-2 30c-2 30c
    212 UGUAAACAUCCCCGACUGGAAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000245 UGUAAACAUCCCCGACUGGAAG  604
    30d 30d 30d
    213 UGUAAACAUCCUUGACUGGAAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000692 UGUAAACAUCCUUGACUGGAAG  605
    30e 30e 30e
    214 AGGCAAGAUGCUGGCAUAGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000089 AGGCAAGAUGCUGGCAUAGCU  606
    31 31 31
    215 UAUUGCACAUUACUAAGUUGCA hsa-mir- hsa-mir- hsa-miR- MIMAT0000090 UAUUGCACAUUACUAAGUUGCA  607
    32 32 32
    216 AAAAGCUGGGUUGAGAGGGCGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000510 AAAAGCUGGGUUGAGAGGGCGA  608
    320a 320a 320a
    217 AAAAGCUGGGUUGAGAGGGCAA hsa-mir- hsa-mir- hsa-miR- MIMAT0005792 AAAAGCUGGGUUGAGAGGGCAA  609
    320b-1 320b-1 320b
    218 AAAAGCUGGGUUGAGAGGGCAA hsa-mir- hsa-mir- hsa-miR- MIMAT0005792 AAAAGCUGGGUUGAGAGGGCAA  610
    320b-2 320b-2 320b
    219 AAAAGCUGGGUUGAGAGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0005793 AAAAGCUGGGUUGAGAGGGU  611
    320c-1 320c-1 320c
    220 AAAAGCUGGGUUGAGAGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0005793 AAAAGCUGGGUUGAGAGGGU  612
    320c-2 320c-2 320c
    221 AAAAGCUGGGUUGAGAGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0006764 AAAAGCUGGGUUGAGAGGA  613
    320d-1 320d-1 320d
    222 AAAAGCUGGGUUGAGAGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0006764 AAAAGCUGGGUUGAGAGGA  614
    320d-2 320d-2 320d
    223 CACAUUACACGGUCGACCUCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000755 CACAUUACACGGUCGACCUCU  615
    323 323 323-3p
    224 CGCAUCCCCUAGGGCAUUGGUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000761 CGCAUCCCCUAGGGCAUUGGUGU  616
    324 324 5324-p
    225 CUGGCCCUCUCUGCCCUUCCGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000752 CUGGCCCUCUCUGCCCUUCCGU  617
    328 328 328
    226 GCAAAGCACACGGCCUGCAGAGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000751 GCAAAGCACACGGCCUGCAGAGA  618
    330 330 330-3p
    227 GCCCCUGGGCCUAUCCUAGAA hsa-mir- hsa-mir- hsa-miR- MIMAT0000760 GCCCCUGGGCCUAUCCUAGAA  619
    331 331 331-3p
    228 UCAAGAGCAAUAACGAAAAAUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000765 UCAAGAGCAAUAACGAAAAAUGU  620
    335 335 335
    229 UCCAGCAUCAGUGAUUUUGUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000763 UCCAGCAUCAGUGAUUUUGUUG  621
    338 338 338-3p
    230 UGAGCGCCUCGACGACAGAGCCG hsa-mir- hsa-mir- hsa-miR- MIMAT0004702 UGAGCGCCUCGACGACAGAGCCG  622
    339-3p 339 339-3p
    231 GUGCAUUGUAGUUGCAUUGCA hsa-mir- hsa-mir- hsa-miR- MIMAT0000091 GUGCAUUGUAGUUGCAUUGCA  623
    33a 33a 33a
    232 GUGCAUUGCUGUUGCAUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003301 GUGCAUUGCUGUUGCAUUGC  624
    33b 33b 33b
    233 UUAUAAAGCAAUGAGACUGAUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004692 UUAUAAAGCAAUGAGACUGAUU  625
    340 340 340
    234 AGGGGUGCUAUCUGUGAUUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004694 AGGGGUGCUAUCUGUGAUUGA  626
    342-5p 342 342-5p
    235 GCUGACUCCUAGUCCAGGGCUC hsa-mir- hsa-mir- hsa-miR- MIMAT0000772 GCUGACUCCUAGUCCAGGGCUC  627
    345 345 345
    236 UGGCAGUGUCUUAGCUGGUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000255 UGGCAGUGUCUUAGCUGGUUGU  628
    34a 34a 34a
    237 AGGCAGUGUCAUUAGCUGAUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000685 UAGGCAGUGUCAUUAGCUGAUUG  629
    34b* 34b 34b*
    238 AGGCAGUGUAGUUAGCUGAUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0000686 AGGCAGUGUAGUUAGCUGAUUGC  630
    34c-5p 34c 34c-5p
    239 UUAUCAGAAUCUCCAGGGGUAC hsa-mir- hsa-mir- hsa-miR- MIMAT0000703 UUAUCAGAAUCUCCAGGGGUAC  631
    361-5p 361 361-5p
    240 AACACACCUAUUCAAGGAUUCA hsa-mir- hsa-mir- hsa-miR- MIMAT0004683 AACACACCUAUUCAAGGAUUCA  632
    362-3p 362 362-3p
    241 AAUUGCACGGUAUCCAUCUGUA hsa-mir- hsa-mir- hsa-miR- MIMAT0000707 AAUUGCACGGUAUCCAUCUGUA  633
    363 363 363
    242 UAAUGCCCCUAAAAAUCCUUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0000710 UAAUGCCCCUAAAAAUCCUUAU  634
    365-2 365-2 365
    243 AAUAAUACAUGGUUGAUCUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000721 AAUAAUACAUGGUUGAUCUUU  635
    369 369 369-3p
    244 GCCUGCUGGGGUGGAACCUGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000722 GCCUGCUGGGGUGGAACCUGGU  636
    370 370 370
    245 ACUCAAACUGUGGGGGCACU hsa-mir- hsa-mir- hsa-miR- MIMAT0004687 ACUCAAACUGUGGGGGCACU  637
    371 371 371-5p
    246 UUAUAAUACAACCUGAUAAGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000727 UUAUAAUACAACCUGAUAAGUG  638
    374a 374a 374a
    247 AUAUAAUACAACCUGCUAAGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0004955 AUAUAAUACAACCUGCUAAGUG  639
    374b 374b 374b
    248 UUUGUUCGUUCGGCUCGCGUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000728 UUUGUUCGUUCGGCUCGCGUGA  640
    375 375 375
    249 AGAGGUUGCCCUUGGUGAAUUC hsa-mir- hsa-mir- hsa-miR- MIMAT0004689 AGAGGUUGCCCUUGGUGAAUUC  641
    377* 377 377*
    250 ACUGGACUUGGAGUCAGAAGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000732 ACUGGACUUGGAGUCAGAAGG  642
    378 378 378
    251 UGGUAGACUAUGGAACGUAGG hsa-mir- hsa-mir- hsa-miR- MIMAT0000733 UGGUAGACUAUGGAACGUAGG  643
    379 379 379
    252 UAUACAAGGGCAAGCUCUCUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000736 UAUACAAGGGCAAGCUCUCUGU  644
    381 381 381
    253 GAAGUUGUUCGUGGUGGAUUCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000737 GAAGUUGUUCGUGGUGGAUUCG  645
    382 382 382
    254 AGAUCAGAAGGUGAUUGUGGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000738 AGAUCAGAAGGUGAUUGUGGCU  646
    383 383 383
    255 CGAAUGUUGCUCGGUGAACCCC hsa-mir- hsa-mir- hsa-miR- MIMAT0001639 GAAUGUUGCUCGGUGAACCCCU  647
    409-3p 409 409-3p
    256 AAUAUAACACAGAUGGCCUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0002171 AAUAUAACACAGAUGGCCUGU  648
    410 410 410
    257 AUAGUAGACCGUAUAGCGUACG hsa-mir- hsa-mir- hsa-miR- MIMAT0003329 UAGUAGACCGUAUAGCGUACG  649
    411 411 411
    258 AUCAACAGACAUUAAUUGGGCGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003339 AUCAACAGACAUUAAUUGGGCGC  650
    421 421 421
    259 UGAGGGGCAGAGAGCGAGACUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004748 UGAGGGGCAGAGAGCGAGACUUU  651
    423 423 423-5p
    260 CAGCAGCAAUUCAUGUUUUGAA hsa-mir- hsa-mir- hsa-miR- MIMAT0001341 CAGCAGCAAUUCAUGUUUUGAA  652
    424 424 424
    261 UAAUACUGUCUGGUAAAACCGU hsa-mir- hsa-mir- hsa-miR- MIMAT0001536 UAAUACUGUCUGGUAAAACCGU  653
    429 429 429
    262 UCUUGGAGUAGGUCAUUGGGUGG hsa-mir- hsa-mir- hsa-miR- MIMAT0002814 UCUUGGAGUAGGUCAUUGGGUGG  654
    432 432 432
    263 AUCAUGAUGGGCUCCUCGGUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0001627 AUCAUGAUGGGCUCCUCGGUGU  655
    433 433 433
    264 UUGCAUAUGUAGGAUGUCCCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0001532 UUGCAUAUGUAGGAUGUCCCAU  656
    448 448 448
    265 UGGCAGUGUAUUGUUAGCUGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0001541 UGGCAGUGUAUUGUUAGCUGGU  657
    449a 449a 449a
    266 AGGCAGUGUAUUGUUAGCUGGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003327 AGGCAGUGUAUUGUUAGCUGGC  658
    449b 449b 449b
    267 UUUUGCGAUGUGUUCCUAAUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0001545 UUUUGCGAUGUGUUCCUAAUAU  659
    450a-1 450a-1 450a
    268 UUUUGCGAUGUGUUCCUAAUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0001545 UUUUGCGAUGUGUUCCUAAUAU  660
    450a-2 450a-2 450a
    269 UUUUGCAAUAUGUUCCUGAAUA hsa-mir- hsa-mir- hsa-miR- MIMAT0004909 UUUUGCAAUAUGUUCCUGAAUA  661
    450b-5p 450b 450b-5p
    270 AACUGUUUGCAGAGGAAACUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0001635 AACUGUUUGCAGAGGAAACUGA  662
    452 452 452
    271 UAGUGCAAUAUUGCUUAUAGGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0003885 UAGUGCAAUAUUGCUUAUAGGGU  663
    454 454 454
    272 GCAGUCCAUGGGCAUAUACAC hsa-mir- hsa-mir- hsa-miR- MIMAT0004784 GCAGUCCAUGGGCAUAUACAC  664
    455-3p 455 455-3p
    273 AAGACGGGAGGAAAGAAGGGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004761 AAGACGGGAGGAAAGAAGGGAG  665
    483-5p 483 483-5p
    274 UCAGGCUCAGUCCCCUCCCGAU hsa-mir- hsa-mir- hsa-miR- MIMAT0002174 UCAGGCUCAGUCCCCUCCCGAU  666
    484 484 484
    275 AGAGGCUGGCCGUGAUGAAUUC hsa-mir- hsa-mir- hsa-miR- MIMAT0002175 AGAGGCUGGCCGUGAUGAAUUC  667
    485-5p 485 485-5p
    276 UCCUGUACUGAGCUGCCCCGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0002177 UCCUGUACUGAGCUGCCCCGAG  668
    486-5p 486 486-5p
    277 AAUCGUACAGGGUCAUCCACUU hsa-mir- hsa-mir- hsa-miR- MIMAT0003180 AAUCGUACAGGGUCAUCCACUU  669
    487b 487b 487b
    278 CCCAGAUAAUGGCACUCUCAA hsa-mir- hsa-mir- hsa-miR- MIMAT0002804 CCCAGAUAAUGGCACUCUCAA  670
    488* 488 488*
    279 UUGUACAUGGUAGGCUUUCAUU hsa-mir- hsa-mir- hsa-miR- MIMAT0002813 UUGUACAUGGUAGGCUUUCAUU  671
    493* 493 493*
    280 UGAAACAUACACGGGAAACCUC hsa-mir- hsa-mir- hsa-miR- MIMAT0002816 UGAAACAUACACGGGAAACCUC  672
    494 494 494
    281 AAACAAACAUGGUGCACUUCUU hsa-mir- hsa-mir- hsa-miR- MIMAT0002817 AAACAAACAUGGUGCACUUCUU  673
    495 495 495
    282 CAGCAGCACACUGUGGUUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0002820 CAGCAGCACACUGUGGUUUGU  674
    497 497 497
    283 UUAAGACUUGCAGUGAUGUUU hsa-mir- hsa-mir- hsa-miR- MIMAT0002870 UUAAGACUUGCAGUGAUGUUU  675
    499-5p 499 499-5p
    284 AUGCACCUGGGCAAGGAUUCUG hsa-mir- hsa-mir- hsa-miR- MIMAT0002871 AUGCACCUGGGCAAGGAUUCUG  676
    500* 500 500*
    285 AAUGCACCCGGGCAAGGAUUCU hsa-mir- hsa-mir- hsa-miR- MIMAT0004774 AAUGCACCCGGGCAAGGAUUCU  677
    501-3p 501 501-3p
    286 AAUGCACCUGGGCAAGGAUUCA hsa-mir- hsa-mir- hsa-miR- MIMAT0004775 AAUGCACCUGGGCAAGGAUUCA  678
    502-3p 502 502-3p
    287 UAGCAGCGGGAACAGUUCUGCAG hsa-mir- hsa-mir- hsa-miR- MIMAT0002874 UAGCAGCGGGAACAGUUCUGCAG  679
    503 503 503
    288 AGACCCUGGUCUGCACUCUAUC hsa-mir- hsa-mir- hsa-miR- MIMAT0002875 AGACCCUGGUCUGCACUCUAUC  680
    504 504 504
    289 GGGAGCCAGGAAGUAUUGAUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0004776 GGGAGCCAGGAAGUAUUGAUGU  681
    505* 505 505*
    290 UGAUUGUAGCCUUUUGGAGUAGA hsa-mir- hsa-mir- hsa-miR- MIMAT0002880 UGAUUGUAGCCUUUUGGAGUAGA  682
    508-3p 508 508-3p
    291 UACUGCAGACGUGGCAAUCAUG hsa-mir- hsa-mir- hsa-miR- MIMAT0004975 UACUGCAGACGUGGCAAUCAUG  683
    509-3-5p 509-3 509-3-5p
    292 UUCACAGGGAGGUGUCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0002877 UUCACAGGGAGGUGUCAU  684
    513a-1 513a-1 513a-5p
    293 UUCACAGGGAGGUGUCAU hsa-mir- hsa-mir- hsa-miR- MIMAT0002877 UUCACAGGGAGGUGUCAU  685
    513a-2 513a-2 513a-5p
    294 UUCACAAGGAGGUGUCAUUUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0005788 UUCACAAGGAGGUGUCAUUUAU  686
    513b 513b 513b
    295 UUCUCAAGGAGGUGUCGUUUAU hsa-mir- hsa-mir- hsa-miR- MIMAT0005789 UUCUCAAGGAGGUGUCGUUUAU  687
    513c 513c 513c
    296 CAUGCCUUGAGUGUAGGACCGU hsa-mir- hsa-mir- hsa-miR- MIMAT0002888 CAUGCCUUGAGUGUAGGACCGU  688
    532 532 532-5p
    297 UGUGACAGAUUGAUAACUGAAA hsa-mir- hsa-mir- hsa-miR- MIMAT0003389 UGUGACAGAUUGAUAACUGAAA  689
    542-3p 542 542-3p
    298 AAACAUUCGCGGUGCACUUCUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004954 AAACAUUCGCGGUGCACUUCUU  690
    543 543 543
    299 CAAAACUGGCAAUUACUUUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003251 CAAAACUGGCAAUUACUUUUGC  691
    548a-1 548a-1 548a-3p
    300 CAAAACUGGCAAUUACUUUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003251 CAAAACUGGCAAUUACUUUUGC  692
    548a-2 548a-2 548a-3p
    301 CAAAACUGGCAAUUACUUUUGC hsa-mir- hsa-mir- hsa-miR- MIMAT0003251 CAAAACUGGCAAUUACUUUUGC  693
    548a-3 548a-3 548a-3p
    302 CAAGAACCUCAGUUGCUUUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0003254 CAAGAACCUCAGUUGCUUUUGU  694
    548b-3p 548b 548b-3p
    303 AAAAACUGAGACUACUUUUGCA hsa-mir- hsa-mir- hsa-miR- MIMAT0005874 AAAAACUGAGACUACUUUUGCA  695
    548e 548e 548e
    304 AAAAGUAAUCGCGGUUUUUGUC hsa-mir- hsa-mir- hsa-miR- MIMAT0005928 AAAAGUAAUCGCGGUUUUUGUC  696
    548h-1 548h-1 548h
    305 AAAAGUAAUCGCGGUUUUUGUC hsa-mir- hsa-mir- hsa-miR- MIMAT0005928 AAAAGUAAUCGCGGUUUUUGUC  697
    548h-2 548h-2 548h
    306 AAAAGUAAUCGCGGUUUUUGUC hsa-mir- hsa-mir- hsa-miR- MIMAT0005928 AAAAGUAAUCGCGGUUUUUGUC  698
    548h-3 548h-3 548h
    307 AAAAGUAAUCGCGGUUUUUGUC hsa-mir- hsa-mir- hsa-miR- MIMAT0005928 AAAAGUAAUCGCGGUUUUUGUC  699
    548h-4 548h-4 548h
    308 AAAAGUAAUUGCGGUCUUUGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0005875 AAAAGUAAUUGCGGUCUUUGGU  700
    548j 548j 548j
    309 AAAAGUACUUGCGGAUUUUGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0005882 AAAAGUACUUGCGGAUUUUGCU  701
    548k 548k 548k
    310 AAAAGUAUUUGCGGGUUUUGUC hsa-mir- hsa-mir- hsa-miR- MIMAT0005889 AAAAGUAUUUGCGGGUUUUGUC  702
    548l 548l 548l
    311 CAAAAGUAAUUGUGGAUUUUGU hsa-mir-  hsa-mir- hsa-miR- MIMAT0005916 CAAAAGUAAUUGUGGAUUUUGU  703
    548n 548n 548n
    312 AGUGCCUGAGGGAGUAAGAGCCC hsa-mir- hsa-mir- hsa-miR- MIMAT0004800 AGUGCCUGAGGGAGUAAGAGCCC  704
    550-1 550-1 550
    313 AGUGCCUGAGGGAGUAAGAGCCC hsa-mir- hsa-mir- hsa-miR- MIMAT0004800 AGUGCCUGAGGGAGUAAGAGCCC  705
    550-2 550-2 550
    314 GCGACCCAUACUUGGUUUCAG hsa-mir- hsa-mir- hsa-miR- MIMAT0003233 GCGACCCAUACUUGGUUUCAG  706
    551b 551b 551b
    315 CACGCUCAUGCACACACCCACA hsa-mir- hsa-mir- hsa-miR- MIMAT0003239 CACGCUCAUGCACACACCCACA  707
    574-3p 574 574-3p
    316 AAGAUGUGGAAAAAUUGGAAUC hsa-mir- hsa-mir- hsa-miR- MIMAT0004796 AAGAUGUGGAAAAAUUGGAAUC  708
    576-3p 576 576-3p
    317 GUAGAUAAAAUAUUGGUACCUG hsa-mir- hsa-mir- hsa-miR- MIMAT0003242 UAGAUAAAAUAUUGGUACCUG  709
    577 577 577
    318 UAACUGGUUGAACAACUGAACC hsa-mir- hsa-mir- hsa-miR- MIMAT0004797 UAACUGGUUGAACAACUGAACC  710
    582-3p 582 582-3p
    319 UUACAGUUGUUCAACCAGUUACU hsa-mir- hsa-mir- hsa-miR- MIMAT0003247 UUACAGUUGUUCAACCAGUUACU  711
    582-5p 582 582-5p
    320 UUAUGGUUUGCCUGGGACUGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0003249 UUAUGGUUUGCCUGGGACUGAG  712
    584 584 584
    321 UGAGAACCACGUCUGCUCUGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004799 UGAGAACCACGUCUGCUCUGAG  713
    589 589 589
    322 UAAUUUUAUGUAUAAGCUAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0004801 UAAUUUUAUGUAUAAGCUAGU  714
    590-3p 590 590-3p
    323 UACGUCAUCGUUGUCAUCGUCA hsa-mir- hsa-mir- hsa-miR- MIMAT0003266 UACGUCAUCGUUGUCAUCGUCA  715
    598 598 598
    324 UCCGAGCCUGGGUCUCCCUCUU hsa-mir- hsa-mir- hsa-miR- MIMAT0003283 UCCGAGCCUGGGUCUCCCUCUU  716
    615-3p 615 615-3p
    325 AAGUCAUUGGAGGGUUUGAGCA hsa-mir- hsa-mir- hsa-miR- MIMAT0004805 AGUCAUUGGAGGGUUUGAGCAG  717
    616 616 616
    326 AAACUCUACUUGUCCUUCUGAGU hsa-mir- hsa-mir- hsa-miR- MIMAT0003287 AAACUCUACUUGUCCUUCUGAGU  718
    618 618 618
    327 AGGGGGAAAGUUCUAUAGUCC hsa-mir- hsa-mir- hsa-miR- MIMAT0003294 AGGGGGAAAGUUCUAUAGUCC  719
    625 625 625
    328 AUGCUGACAUAUUUACUAGAGG hsa-mir- hsa-mir- hsa-miR- MIMAT0004809 AUGCUGACAUAUUUACUAGAGG  720
    628-5p 628 628-5p
    329 UGGGUUUACGUUGGGAGAACU hsa-mir- hsa-mir- hsa-miR- MIMAT0004810 UGGGUUUACGUUGGGAGAACU  721
    629 629 629
    330 AAAGACAUAGGAUAGAGUCACCUC hsa-mir- hsa-mir- hsa-miR- MIMAT0003311 AAAGACAUAGGAUAGAGUCACCUC  722
    641 641 641
    331 ACACUUGUAUGCUAGCUCAGGU hsa-mir- hsa-mir- hsa-miR- MIMAT0003313 ACUUGUAUGCUAGCUCAGGUAG  723
    643 643 643
    332 UUUAGGAUAAGCUUGACUUUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0003321 UUUAGGAUAAGCUUGACUUUUG  724
    651 651 651
    333 AAUGGCGCCACUAGGGUUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0003322 AAUGGCGCCACUAGGGUUGUG  725
    652 652 652
    334 UAUGUCUGCUGACCAUCACCUU hsa-mir- hsa-mir- hsa-miR- MIMAT0004814 UAUGUCUGCUGACCAUCACCUU  726
    654-3p 654 654-3p
    335 UACCCAUUGCAUAUCGGAGUUG hsa-mir- hsa-mir- hsa-miR- MIMAT0003338 UACCCAUUGCAUAUCGGAGUUG  727
    660 660 660
    336 UCCGGUUCUCAGGGCUCCACC hsa-mir- hsa-mir- hsa-miR- MIMAT0004819 UCCGGUUCUCAGGGCUCCACC  728
    671-3p 671 671-3p
    337 AAGGAGCUUACAAUCUAGCUGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0004926 AAGGAGCUUACAAUCUAGCUGGG  729
    708 708 708
    338 UGGAAGACUAGUGAUUUUGUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000252 UGGAAGACUAGUGAUUUUGUUGU  730
    7-1 7-1 7
    339 UGGAAGACUAGUGAUUUUGUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000252 UGGAAGACUAGUGAUUUUGUUGU  731
    7-2 7-2 7
    340 UGGAAGACUAGUGAUUUUGUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000252 UGGAAGACUAGUGAUUUUGUUGU  732
    7-3 7-3 7
    341 CGGCUCUGGGUCUGUGGGGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004957 CGGCUCUGGGUCUGUGGGGA  733
    760 760 760
    342 UGCACCAUGGUUGUCUGAGCAUG hsa-mir- hsa-mir- hsa-miR- MIMAT0003882 UGCACCAUGGUUGUCUGAGCAUG  734
    767-5p 767 767-5p
    343 UGAGACCUCUGGGUUCUGAGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0003886 UGAGACCUCUGGGUUCUGAGCU  735
    769-5p 769 769-5p
    344 GCAGGAACUUGUGAGUCUCCU hsa-mir- hsa-mir- hsa-miR- MIMAT0004953 GCAGGAACUUGUGAGUCUCCU  736
    873 873 873
    345 CUGCCCUGGCCCGAGGGACCGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004911 CUGCCCUGGCCCGAGGGACCGA  737
    874 874 874
    346 GUAGAGGAGAUGGCGCAGGG hsa-mir- hsa-mir- hsa-miR- MIMAT0004949 GUAGAGGAGAUGGCGCAGGG  738
    877 877 877
    347 GUGAACGGGCGCCAUCCCGAGG hsa-mir- hsa-mir- hsa-miR- MIMAT0004951 GUGAACGGGCGCCAUCCCGAGG  739
    887 887 887
    348 UUAAUAUCGGACAACCAUUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0004921 UUAAUAUCGGACAACCAUUGU  740
    889 889 889
    349 UGCAACGAACCUGAGCCACUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0004902 UGCAACGAACCUGAGCCACUGA  741
    891a 891a 891a
    350 CACUGUGUCCUUUCUGCGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004907 CACUGUGUCCUUUCUGCGUAG  742
    892a 892a 892a
    351 UCUUUGGUUAUCUAGCUGUAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000441 UCUUUGGUUAUCUAGCUGUAUGA  743
    9-1 9-1 9
    352 UCUUUGGUUAUCUAGCUGUAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000441 UCUUUGGUUAUCUAGCUGUAUGA  744
    9-2 9-2 9
    353 UAUUGCACUUGUCCCGGCCUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000092 UAUUGCACUUGUCCCGGCCUGU  745
    92a-1 92a-1 92a
    354 UAUUGCACUUGUCCCGGCCUGU hsa-mir- hsa-mir- hsa-miR- MIMAT0000092 UAUUGCACUUGUCCCGGCCUGU  746
    92a-2 92a-2 92a
    355 UAUUGCACUCGUCCCGGCCUCC hsa-mir- hsa-mir- hsa-miR- MIMAT0003218 UAUUGCACUCGUCCCGGCCUCC  747
    92b 92b 92b
    356 CAAAGUGCUGUUCGUGCAGGUAG hsa-mir- hsa-mir- hsa-miR- MIMAT0000093 CAAAGUGCUGUUCGUGCAGGUAG  748
    93 93 93
    357 UCUUUGGUUAUCUAGCUGUAUGA hsa-mir- hsa-mir- hsa-miR- MIMAT0000441 UCUUUGGUUAUCUAGCUGUAUGA  749
    9-3 9-3 9
    358 AAGGCAGGGCCCCCGCUCCCC hsa-mir- hsa-mir- hsa-miR- MIMAT0004983 AAGGCAGGGCCCCCGCUCCCC  750
    940 940 940
    359 UUCUCUGUUUUGGCCAUGUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0004985 UCUUCUCUGUUUUGGCCAUGUG  751
    942 942 942
    360 AAAUUAUUGUACAUCGGAUGAG hsa-mir- hsa-mir- hsa-miR- MIMAT0004987 AAAUUAUUGUACAUCGGAUGAG  752
    944 944 944
    361 UUCAACGGGUAUUUAUUGAGCA hsa-mir- hsa-mir- hsa-miR- MIMAT0000094 UUCAACGGGUAUUUAUUGAGCA  753
    95 95 95
    362 UUUGGCACUAGCACAUUUUUGCU hsa-mir- hsa-mir- hsa-miR- MIMAT0000095 UUUGGCACUAGCACAUUUUUGCU  754
    96 96 96
    363 UGAGGUAGUAAGUUGUAUUGUU hsa-mir- hsa-mir- hsa-miR- MIMAT0000096 UGAGGUAGUAAGUUGUAUUGUU  755
    98 98 98
    364 AACCCGUAGAUCCGAUCUUGUG hsa-mir- hsa-mir- hsa-miR- MIMAT0000097 AACCCGUAGAUCCGAUCUUGUG  756
    99a 99a 99a
    365 CACCCGUAGAACCGACCUUGCG hsa-mir- hsa-mir- hsa-miR- MIMAT0000689 CACCCGUAGAACCGACCUUGCG  757
    99b 99b 99b
    366 AACAUAGAGGAAAUUCCACGU hsa-mir- hsa-mir- hsa-mir- AACAUAGAGGAAAUUCCACGU  758
    376c 376c 376c
    367 AUCAUAGAGGAAAAUCCAUGUU hsa-mir- hsa-mir- hsa-mir- AUCAUAGAGGAAAAUCCAUGUU  759
    376b 376b 376b
    368 UGGUGGGCCGCAGAACAUGUGC hsa-mir- hsa-mir- hsa-mir- UGGUGGGCCGCAGAACAUGUGC  760
    654 654 654
    369 AUCAUAGAGGAAAAUCCACGU hsa-mir- hsa-mir- hsa-mir- AUCAUAGAGGAAAAUCCACGU  761
    376a-2 376a-2 376a-2
    370 AUCAUAGAGGAAAAUCCACGU hsa-mir- hsa-mir- hsa-mir- AUCAUAGAGGAAAAUCCACGU  762
    376a-1 376a-1 376a-1
    371 AAAACCGUCUAGUUACAGUUGU hsa-mir-
    1537
    372 AUAUACAGGGGGAGACUCUCAU hsa-mir-
    1185-2
    373 CCUAGAAUGGGGAUUGUGGG hsa-mir-
    1301*
    374 AGCGAGACCUCAACUCUACAAU hsa-mir-
    1303
    375 UCGACCGGACCUCGACCGGCUC hsa-mir-
    1307*
    376 AUGUAGGGAUGGAAGCCAUGAA hsa-mir-
    135a-2
    377 CUCACUGAACAAUGAAUGCAA hsa-mir-
    181b-1*
    378 CGGGUAGAGAGGGCAGUGGGAG hsa-mir-
    197*
    379 GCUGGGAAGGCAAAGGGACGU hsa-mir-
    204*
    380 ACCUUGGCUCUAGACUGCUUAC hsa-mir-
    212*
    381 GCUCUGACUUUAUUGCACUACU hsa-mir-
    301a
    382 AGGGACUUUUGGGGGCAGAUGU hsa-mir-
    365-1
    383 UUGGGGACAUUUUGCAUUCAU hsa-mir-
    450a-2*
    384 AAUGUGUAGCAAAAGACAGA hsa-mir-
    511-1-3p
    385 AAUGUGUAGCAAAAGACAGA hsa-mir-
    511-2-3p
    386 AUCAUACAAGGACAAUUUCUUU hsa-mir-
    539
    387 AAAGGUAAUUGCAGUUUUUCCC hsa-mir-
    570
    388 UCGCGGUUUGUGCCAGAUGACG hsa-mir-
    579
    389 AGAAGGCACUAUGAGAUUUAGA hsa-mir-
    605
    390 AGACACAUUUGGAGAGGGAACC hsa-mir-
    642
    391 AGGACCUUCCCUGAACCAAGGA hsa-mir-
    659
    392 AUAUACAGGGGGAGACUCUUAU hsa-mir-
    1185-1
  • TABLE 32
    Novel miRNAs identified by deep sequencing analysis.
    SEQ Temporary SEQ
    ID Mature Assigned miRBase ID
    NO. Sequence Captured miRNA ID ID NO. miRNA Precursor Sequence
    763 CCAAAACUGCAGUUACUUUUG has-mir-548o- pending 1057 UggUgcaaaagUaaUUgcggUUUUUgccaUUaaaagUaaUgc
    2 ggCCAAAACUGCAGUUACUUUUGcaccc
    764 GAGCCUGGAAGCUGGAGCCUGC hsa-mir-1254- hsa-mir- 1058 cUGAGCCUGGAAGCUGGAGCCUGCagUgagcUaUgaUca
    2 1254-2 UgUcccUgUacUcUagccUgggca
    765 CGGGCGUGGUGGUGGGGGUG hsa-mir-1268b hsa-mir- 1059 accCGGGCGUGGUGGUGGGGGUGggUgccUgUaaUUcca
    1268b gcUagUUggga
    766 UCGAGGAGCUCACAGUCUAGA hsa-miR-151- hsa-mir- 1060 agUcUcUcUUcagggcUcccgagacacagaaacagacaccUgccc
    5p-2 151b UCGAGGAGCUCACAGUCUAGAca
    767 UAAGGUGCAUCUAGUGCAGUU hsa-mir-18b- hsa-mir- 1061 UcUUgUgUUAAGGUGCAUCUAGUGCAGUUagUgaagcag
    2 18b cUUagaaUcUacUgcccUaaaUgccccUUcUggcacaggc
    768 GAGGGUUGGGUGGAGGC hsa-miR-296- hsa-miR- 1062 cUgccUccaccccgccUggccUgacccagccagggcUcUagGAGG
    2 296-2 GUUGGGUGGAGGCaa
    769 AUCAUAGAGGAAAAUCCAUGUU hsa-mir-376b- hsa-mir- 1063 UaaaacgUggaUaUUccUUcUaUgUUUacgUgaUUccUggU
    2 376b UaAUCAUAGAGGAAAAUCCAUGUUUUc
    770 AACAUAGAGGAAAUUCCACGU hsa-mir-376c- hsa-mir- 1064 UaaaaggUggaUaUUccUUcUaUgUUUaUgUUaUUUaUgg
    2 376c UUaAACAUAGAGGAAAUUCCACGUUUUc
    771 ACUGGACUUGGAGUCAGAAA hsa-mir-378b- hsa-mir- 1065 acUgUUUcUgUccUUgUUcUUgUUgUUaUUACUGGACU
    1 378d-1 UGGAGUCAGAAAcagg
    772 ACUGGACUUGGAGUCAGAAA hsa-mir-378b- hsa-mir- 1066 aggagagaacACUGGACUUGGAGUCAGAAAacUUUcaUcc
    2 378d-2 aagUcaUUcccUgcUcUaagUcccaUUUcUgUUcca
    773 ACUGGACUUGGAGUCAGGA hsa-miR-378c hsa-mir- 1067 cUgacUccagUgUccaggccaggggcagacagUggacagagaacag
    378e UgcccaagaccACUGGACUUGGAGUCAGGAcaU
    774 AGGCAGUGUAUUGCUAGCGGCU hsa-mir-449c hsa-mir- 1068 UcaggUAGGCAGUGUAUUGCUAGCGGCUgUUaaUgaUU
    449c UUaacagUUgcUagUUgcacUccUcUcUgU
    775 UGCACCCAGGCAAGGAUUCUGC hsa-mir-500- hsa-mir- 1069 gUUcccccUcUcUaaUccUUgcUaccUgggUgagagUgcUUUc
    2 500b UgaaUgcagUGCACCCAGGCAAGGAUUCUGCaagggggag
    U
    776 UAAUCCUUGCUACCUGGGUGAG hsa-mir-500- has-mir- 1070 gUUcccccUcUcUAAUCCUUGCUACCUGGGUGAGagUgc
    2* 500b UUUcUgaaUgcagUgcacccaggcaaggaUUcUgcaagggggag
    U
    777 AAAAGUAAUCGCGGUUUUUGUC hsa-mir-548h- hsa-mir- 1071 acAAAAGUAAUCGCGGUUUUUGUCaUUacUUUUaacUg
    5 548h-5 UaaaaaccacggUUgcUUUUgc
    778 AAAAGUAAUUGUGGAUUUUGCU hsa-mir-548r- hsa-mir- 1072 aUgUUggUgcAAAAGUAAUUGUGGAUUUUGCUaUUacU
    1 548ab UgUaUUUaUUUgUaaUgcaaaacccgcaaUUagUUUUgcacc
    aacc
    779 AAAAGUAAUUGUGGAUUUUGCU hsa-mir-548r- has-mir- 1073 UgUUggUgcAAAAGUAAUUGUGGAUUUUGCUaUUacU
    2 548ab UgUaUUUaUUUgUaaUgcaaaacccgcaaUUagUUUUgcacc
    aacc
    780 UGUCUUACUCCCUCAGGCACAU hsa-miR-550- pending 1074 cUggUgcagUgccUgagggagUaagagUccUgUUgUUgUaaga
    3* UagUGUCUUACUCCCUCAGGCACAUcUccaa
    781 GGUGGGCUUCCCGGAGGG hsa-mir-2221 hsa-mir- 1075 gaaaacaaccaGGUGGGCUUCCCGGAGGGcggaacacccagc
    4417 cccagcaUccagggcUcaccUaccacgUUUg
    782 GAAGCGGUGGCUGGGCUG hsa-mir-2222 pending 1076 gaggcggcccUagcgccaUUUUgUgggagcGAAGCGGUGGCU
    GGGCUGcgcUUg
    783 CACUGCAGGACUCAGCAG hsa-mir-2223 hsa-mir- 1077 UggUUUUUgcUcUgagUgaccgUggUggUUgUgggagUCAC
    4418 UGCAGGACUCAGCAGgaaUUc
    784 UGAGGGAGGAGACUGCA hsa-mir-2224 hsa-mir- 1078 UggUggUgUgUgccUgUagUcUUagcUacUcgggaggcUGAG
    4419a GGAGGAGACUGCAgUgagUggaggUcacgccacUg
    785 ACUGGACUUGGAGCCAGAAG hsa-mir-2225 hsa-mir- 1079 gUcaggUccUggacUcccaUagUUUUcaggcUgcUaaacaacag
    378f aacgagcACUGGACUUGGAGCCAGAAGUcUUggg
    786 GUCACUGAUGUCUGUAGCUGAG hsa-mir-2226 hsa-mir- 1080 cUcUUggUaUgaacaUcUgUgUgUUcaUgUcUcUcUgUgca
    4420 caggggacgagaGUCACUGAUGUCUGUAGCUGAGac
    787 GAUGAGGAUGGAUAGCAAGGAA hsa-mir-2227 hsa-mir- 1081 cUggccUcUgUgccUggaUacUUUaUacgUgUaaUUgUGAU
    3605 GAGGAUGGAUAGCAAGGAAgccgc
    788 ACCUGUCUGUGGAAAGGAGCUA hsa-mir-2228 hsa-mir- 1082 cUgggUcUccUUUcUgcUgagagUUgaacacUUgUUgggaca
    4421 ACCUGUCUGUGGAAAGGAGCUAccUac
    789 AAAAGCAUCAGGAAGUACCCA hsa-mir-2229 hsa-mir- 1083 agUUcUUcUgcagacAAAAGCAUCAGGAAGUACCCAccaU
    4422 gUaccagUgggcccUUcUUgaUgcUcUUgaUUgcagaggagcc
    790 UGCCUGGAACAUAGUAGGGACU hsa-mir-2230- hsa-mir- 1084 UccUUUaUUgagUcccUacUaUgUUccaggcaccUacgaUacc
    1 3116-2 cagUGCCUGGAACAUAGUAGGGACUcaaUaaagU
    791 UGCCUGGAACAUAGUAGGGACU hsa-mir-2230- hsa-mir- 1085 ccUUUaUUgagUcccUacUaUgUUccaggcaccUacgaUaccc
    2 3116-1 agUGCCUGGAACAUAGUAGGGACUcaaUaaagU
    792 UGGAUUAAAAACAAUGGAGG hsa-mir-2231 pending 1086 cgccUccaUgUUUcagcaUcUaUgUcaUgggcUUggUccUgga
    gUGGAUUAAAAACAAUGGAGGU
    793 AUAGGCACCAAAAAGCAACAA hsa-mir-2232 hsa-mir- 1087 aUcaUgUacUgcagUUgccUUUUUgUUcccaUgcUgUUUaa
    4423 gccUagcAUAGGCACCAAAAAGCAACAAcagUaUgUgaa
    794 ACUGGGCUUGGAGUCAGAAG hsa-mir-2233 hsa-mir- 1088 cACUGGGCUUGGAGUCAGAAGaccUggcUccagcccagcUc
    378g gUaUUaggUUggUgcaaaagUUaUUgUggUUUUUgcUaUU
    795 CAAAAACCGGCAAUUACUUUUG hsa-mir-2234 hsa-mir- 1089 UUUUUUUaaUggCAAAAACCGGCAAUUACUUUUGcacU
    548ac aaccUagUag
    796 GUCAAAUGAAGGGCUGAUCACG hsa-mir-2235 pending 1090 aaagUGUCAAAUGAAGGGCUGAUCACGaaaUagcgcaUU
    agcUcUUUUUUUgaaaacUUg
    797 AAAGGGAGGAUUUGCUUAGAAGG hsa-mir-2236 pending 1091 gacUggcUacgUagUUcgggcaaaUccUccaaaagggAAAGGG
    AUGG AGGAUUUGCUUAGAAGGAUGGcgcUcc
    798 AGAGUUAACUCAAAAUGGACUA hsa-mir-2237 hsa-mir- 1092 cUUacaUcacacacAGAGUUAACUCAAAAUGGACUAaUU
    4424 UUUccacUagUUagUccaUUUcaagUUaacUcUgUgUgUga
    UgUagU
    799 UGUUGGGAUUCAGCAGGACCAU hsa-mir-2238 hsa-mir- 1093 gUgcUUUacaUgaaUggUcccaUUgaaUcccaacagcUUUgcg
    4425 aagUgUUGUUGGGAUUCAGCAGGACCAUUcgUgUaaag
    Uaa
    800 UAAAUAGAGUAGGCAAAGGACA hsa-mir-2239 hsa-mir- 1094 UaaaUggUUaUgUccUUUgccUaUUcUaUUUaagacacccU
    3121 gUaccUUAAAUAGAGUAGGCAAAGGACAgaaacaUUUU
    801 AGAGUCGAGAGUGGGAGAAGAG hsa-mir-2240 pending 1095 gcAGAGUCGAGAGUGGGAGAAGAGcggagcgUgUgagcag
    UacUgcggccUccUcUccUcUccUaaccUcgcUcUc
    802 GAAGAUGGACGUACUUU hsa-mir-2241 hsa-mir- 1096 agUUGAAGAUGGACGUACUUUgUcUgacUacaaUaUUca
    4426 aaaggagUcUacUcUUcaUcUUg
    803 UCUGAAUAGAGUCUGAAGAGU hsa-mir-2242 hsa-mir- 1097 gaagccUcUUggggcUUaUUUagacaaUggUUUcaUcaUUUc
    4427 gUCUGAAUAGAGUCUGAAGAGUcUUU
    804 CAAGGAGACGGGAACAUGGAGC hsa-mir-2243 hsa-mir- 1098 UUggcaggUgccaUgUUgccUgcUccUUacUgUacacgUggcU
    4428 ggCAAGGAGACGGGAACAUGGAGCcgccaU
    805 AAGAGGAAGAAAUGGCUGGUUC hsa-mir-2244 hsa-mir- 1099 aggaagAAGAGGAAGAAAUGGCUGGUUCUcaggUgaaUg
    3916 UgUcUgggUUcaggggaUgUgUcUccUcUUUUcU
    806 UUCGCGGGCGAAGGCAAAGUC hsa-mir-2245 hsa-mir- 1100 ggcgggcUUCGCGGGCGAAGGCAAAGUCgaUUUccaaaag
    3124 UgacUUUccUcacUcccgUgaagUcggcg
    807 AAAAGCUGGGCUGAGAGGCG hsa-mir-2246 hsa-mir- 1101 agggagAAAAGCUGGGCUGAGAGGCGacUggUgUcUaaU
    4429 UUgUUUgUcUcUccaacUcagacUgccUggccca
    808 AUGGCCAAAACUGCAGUUAUUU hsa-mir-2247 hsa-mir- 1102 cUgcaaaaaUaaUUgcagUUUUUgccaUUaUUUUUaaUaa
    548s UUaUaaUaAUGGCCAAAACUGCAGUUAUUUUUgcac
    809 UAGUGGAUGAUGCACUCUGUGC hsa-mir-2248 hsa-mir- 1103 cUacUUccagUAGUGGAUGAUGCACUCUGUGCagggccaa
    3681 cUgUgcacacagUgcUUcaUccacUacUggaagUgU
    810 AGGCUGGAGUGAGCGGAG hsa-mir-2249 hsa-mir- 1104 gUgAGGCUGGAGUGAGCGGAGaUcgUaccacUgcacUcca
    4430 accUggUga
    811 GAAAACGACAAUGACUUUUGCA hsa-mir-2250 hsa-mir- 1105 cUgUUaggUUggUgcaaaagUaaUUgUggUUUUUgaaagUa
    548ad acUUggcGAAAACGACAAUGACUUUUGCAccaaUcUaaUa
    c
    812 GCGACUCUGAAAACUAGAAGGU hsa-mir-2251 hsa-mir- 1106 UggUUUGCGACUCUGAAAACUAGAAGGUUUaUgacUgg
    4431 gcaUUUcUcacccaaUgcccaaUaUUgaacUUUcUagUUgUc
    agagUcaUUaaccc
    813 AGAAGGCUGGAGCGCGGCGGU hsa-mir-2252 pending 1107 gcacUgcggUUcUgaggccgUUacUccggcUUcUccaUagaggg
    cggAGAAGGCUGGAGCGCGGCGGUga
    814 AAAGACUCUGCAAGAUGCCU hsa-mir-2253 hsa-mir- 1108 gcaUcUUgcagagccgUUccaaUgcgacaccUcUagagUgUcaU
    4432 ccccUagaaUgUcaccUUggAAAGACUCUGCAAGAUGCCU
    815 ACAGGAGUGGGGGUGGGACAU hsa-mir-2254 hsa-mir- 1109 caUccUccUUacgUcccaccccccacUccUgUUUcUggUgaaaU
    4433 aUUcaaACAGGAGUGGGGGUGGGACAUaaggaggaUa
    816 AGGAGAAGUAAAGUAGAA hsa-mir-2255 hsa-mir- 1110 UcacUUUAGGAGAAGUAAAGUAGAAcUUUggUUUUcaa
    4434 cUUUUccUacagUgU
    817 AUGGCCAGAGCUCACACAGAGG hsa-mir-2256 hsa-mir- 1111 aggcagcaaAUGGCCAGAGCUCACACAGAGGgaUgagUgca
    4435-1 cUUcaccUgcagUgUgacUcagcaggccaacagaUgcUa
    818 GCAGGACAGGCAGAAGUGGAU hsa-mir-2257 hsa-mir- 1112 gccUcacUUUUccacUUaUgccUgcccUgccccUcgaaUcUgcU
    4436 ccacgaUUUggGCAGGACAGGCAGAAGUGGAUaagUgagg
    a
    819 AUCAGGGCUUGUGGAAUGGGAA hsa-mir-2258 hsa-mir- 1113 ggcccAUCAGGGCUUGUGGAAUGGGAAggagaagggacgc
    3127 UUccccUUcUgcaggccUgcUgggUg
    820 AUGGCCAGAGCUCACACAGAGG hsa-mir-2259 hsa-mir- 1114 gcaaAUGGCCAGAGCUCACACAGAGGgaUgagUgcacUUc
    4435-2 accUgcagUgUgacUcagcaggccaacagaUgcU
    821 UGAGGAUAUGGCAGGGAAGGGG hsa-mir-2260 hsa-mir- 1115 acgUggUGAGGAUAUGGCAGGGAAGGGGagUUUcccUc
    3679 UaUUcccUUccccccagUaaUcUUcaUcaUgc
    822 AGGAGGUUGGUGUGGAUU hsa-mir-2261 pending 1116 UaUgAGGAGGUUGGUGUGGAUUcUgUUgaagaaaaagaa
    ggggaacacUaaUUUUccaUU
    823 UUGGAAGACAUGGAGCAUGAGG hsa-mir-2262 pending 1117 UUUUGGAAGACAUGGAGCAUGAGGUaagUgccUagaUcc
    UcaaaccacUUgccUccaccUaUgcUUccaggU
    824 UCUGGCAAGUAAAAAACUCUCA hsa-mir-2263 hsa-mir- 1118 cUUccUCUGGCAAGUAAAAAACUCUCAUUUUccUUaaaa
    3128 aaUgagagUUUUUUacUUgcaaUaggaaa
    825 UGGGCUCAGGGUACAAAGGUU hsa-mir-2264 hsa-mir- 1119 acUUUgUgcaUUgggUccacaaggaggggaUgacccUUgUGG
    4437 GCUCAGGGUACAAAGGUU
    826 CAAAAACUGCAAUUACUUUCA hsa-mir-2265- hsa-mir- 1120 gcagUUUUUgccaUUaagUUgcggUUUUUgccaUUaUaaUg
    1 548ae-1 gCAAAAACUGCAAUUACUUUCAcaccUgc
    827 CAAAAACUGCAAUUACUUUCA hsa-mir-2265- hsa-mir- 1121 UgUgcaaaagUaaUUgUggUUUUUgUcaUUUaaaagUaaUg
    2 548ae-2 gCAAAAACUGCAAUUACUUUCAcacc
    828 GCUGCACCGGAGACUGGGUAA hsa-mir-2266- hsa-mir- 1122 acUUgUcaUgUcUUacccagUcUccggUgcagccUgUUgUcaa
    1 3130-1 gGCUGCACCGGAGACUGGGUAAgacaUgacaagc
    829 GCUGCACCGGAGACUGGGUAA hsa-mir-2266- hsa-mir- 1123 UgUcUUacccagUcUccggUgcagccUUgacaacagGCUGCAC
    2 3130-2 CGGAGACUGGGUAAgacaUgacaagUU
    830 AUCCCCAGAUACAAUGGACAAU hsa-mir-2267 hsa-mir- 1124 cgUgUcAUCCCCAGAUACAAUGGACAAUaUgcUaUUaUa
    2355 aUcgUaUggcaUUgUccUUgcUgUUUggagaUaaUacU
    831 AUUGUCCUUGCUGUUUGGAGAU hsa-mir-2267* pending 1125 cgUgUcaUccccagaUacaaUggacaaUaUgcUaUUaUaaUcg
    UaUggcAUUGUCCUUGCUGUUUGGAGAUaaUacU
    832 CACAGGCUUAGAAAAGACAGU hsa-mir-2268 hsa-mir- 1126 UaagUgUaaacUUaaggacUgUcUUUUcUaagccUgUgccUU
    4438 gccUUUccUUUggCACAGGCUUAGAAAAGACAGUcUUUa
    agUUUacacUUc
    833 UCGAGGACUGGUGGAAGGGCCU hsa-mir-2269 hsa-mir- 1127 UcUcagagUCGAGGACUGGUGGAAGGGCCUUUccccUca
    3131 gaccaaggcccUggccccagcUUcUUcUcagagU
    834 GUGACUGAUACCUUGGAGGCAU hsa-mir-2270 hsa-mir- 1128 ccaGUGACUGAUACCUUGGAGGCAUUUUaUcUaagaUac
    4439 acacaaagcaaaUgccUcUaaggUaUcagUUUaccaggcca
    835 AGGGCUGGACUCAGCGGCGGAG hsa-mir-2271 pending 1129 gcgcagAGGGCUGGACUCAGCGGCGGAGcUggcUgcUggc
    cUcagUUcUgccUcUgUccaggUccUUgUga
    836 UGUCGUGGGGCUUGCUGGCUUG hsa-mir-2272 hsa-mir- 1130 cUcUcaccaagcaagUgcagUggggcUUgcUggcUUgcaccgUg
    4440 acUcccUcUcaccaagcaagUGUCGUGGGGCUUGCUGGCU
    UGcacUgUgaagaU
    837 ACAGGGAGGAGAUUGUA hsa-mir-2273 hsa-mir- 1131 cagagUcUccUUcgUgUacagggaggagacUgUacgUgagagaU
    4441 agUcagaUccgcaUgUUagagcagagUcUccUUcgUgUACAG
    GGAGGAGAUUGUAc
    838 ACUGGACUUGGAGGCAGAA hsa-mir-2274 hsa-mir- 1132 UggUcaUUgagUcUUcaaggcUagUggaaagagcACUGGACU
    378b UGGAGGCAGAAagaccc
    839 GCCGGACAAGAGGGAGG hsa-mir-2275 hsa-mir- 1133 gcgcccUcccUcUcUccccggUgUgcaaaUgUgUgUgUgcggUg
    4442 UUaUGCCGGACAAGAGGGAGGUg
    840 AUACACAUACACGCAACACACA hsa-mir-2276 hsa-mir- 1134 aUgUgUgUgUaUaUgUgUgUUgcaUgUgUgUaUaUgUgUg
    466 UaUaUaUgUacacAUACACAUACACGCAACACACAUaUa
    UacaUgcac
    841 UUGGAGGCGUGGGUUUU hsa-mir-2277 hsa-mir- 1135 ggUgggggUUGGAGGCGUGGGUUUUagaaccUaUcccUU
    4443 UcUagcccUgagca
    842 AAUUCCCUUGUAGAUAACCCGG hsa-mir-2278 hsa-mir- 1136 cgaUcacUagaUUaUcUacaagggaaUUUUUUUUUaaUUU
    3938 aaaaAAUUCCCUUGUAGAUAACCCGGUggUca
    843 AAGACUGGAGACAAAGUGGGAG hsa-mir-2279 pending 1137 CACCACCAAAAUCUCCAGGGGCAUCGUUGAAAUCGUA
    AGGGAUGUGCAGCUCAUUAAGACUGGAGACAAAGUG
    GGAG
    844 CUGACUGAAUAGGUAGGGUCAU hsa-mir-2280 hsa-mir- 1138 aaaCUGACUGAAUAGGUAGGGUCAUUUUUcUgUgacUg
    3136 cacaUggcccaaccUaUUcagUUagUUc
    845 CUCGAGUUGGAAGAGGCG hsa-mir-2281 hsa-mir- 1139 gUgacgacUggccccgccUcUUccUcUcggUcccaUaUUgaaCU
    4444 CGAGUUGGAAGAGGCGagUccggUcUcaaa
    846 AGAUUGUUUCUUUUGCCGUGCA hsa-mir-2282 hsa-mir- 1140 UUccUgcAGAUUGUUUCUUUUGCCGUGCAagUUUaagU
    4445 UUUUgcacggcaaaagaaacaaUccagagggU
    847 CACGGCAAAAGAAACAAUCCA hsa-mir-2282* has-mir- 1141 UUccUgcagaUUgUUUcUUUUgccgUgcaagUUUaagUUU
    4445 UUgCACGGCAAAAGAAACAAUCCAgagggU
    848 CAGGGCUGGCAGUGACAUGGGU hsa-mir-2283 hsa-mir- 1142 cUggUccaUUUcccUgccaUUcccUUggcUUcaaUUUacUcc
    4446 CAGGGCUGGCAGUGACAUGGGUcaa
    849 GGUGGGGGCUGUUGUUU hsa-mir-2284 hsa-mir- 1143 gUUcUagagcaUggUUUcUcaUcaUUUgcacUacUgaUacU
    4447 UggggUcagaUaaUUgUUUgUGGUGGGGGCUGUUGUUU
    gcaUUgUaggaU
    850 UGGGGAGGUGUGGAGUCAGCAU hsa-mir-2285 pending 1144 gggcaUGGGGAGGUGUGGAGUCAGCAUggggcUaggaggc
    cccgcgcUgacccgccUUcUccgcagcUg
    accUgagcaccaUUUacUgagUccUUUgUUcUcUacUagUUU
    851 GCAGAGAACAAAGGACUCAGU hsa-mir-2286 hsa-mir- 1145 gUagUagUUcgUaGCAGAGAACAAAGGACUCAGUaaaUg
    3919 gUgcUcagga
    852 GGCUCCUUGGUCUAGGGGUA hsa-mir-2287 hsa-mir- 1146 aggagUgaccaaaagacaagagUgcgagccUUcUaUUaUgcccag
    4448 acagggccaccagagGGCUCCUUGGUCUAGGGGUAaUgcca
    853 CGUCCCGGGGCUGCGCGAGGCA hsa-mir-2288 hsa-mir- 1147 agcagcccUcggcggcccggggggcgggcggcggUgccCGUCCCG
    4449 GGGCUGCGCGAGGCAcaggcg
    854 AAAGGUAAUUGUGGUUUCUGC hsa-mir-2289- hsa-mir- 1148 gUgcAAAGGUAAUUGUGGUUUCUGCUUUUaaaggUaaU
    1 548ag-1 ggcaaaUaUUacaUUUacUUUUgcacca
    855 AAAGGUAAUUGUGGUUUCUGC hsa-mir-2289- hsa-mir- 1149 UgcAAAGGUAAUUGUGGUUUCUGCcaUUgaaagUaaagg
    2 548ag-2 caagaaccUcaaUUaccUUUgcagc
    856 UGGGGAUUUGGAGAAGUGGUGA hsa-mir-2290 hsa-mir- 1150 UgUcUGGGGAUUUGGAGAAGUGGUGAgcgcaggUcUUU
    4450 ggcaccaUcUccccUggUcccUUggcU
    857 AAAAGUGAUUGCAGUGUUUG hsa-mir-2291 hsa-mir- 1151 aggUUggUgcAAAAGUGAUUGCAGUGUUUGccaaUaaaa
    548ah gUaaUgacaaaaacUgcagUUacUUUUgcaccagccc
    858 UGGUAGAGCUGAGGACA hsa-mir-2292 hsa-mir- 1152 UcUgUaccUcagcUUUgcUcccaaccaaccacUUccacaUgUU
    4451 UUgcUGGUAGAGCUGAGGACAgc
    859 UUGAAUUCUUGGCCUUAAGUGAU hsa-mir-2293 hsa-mir- 1153 UggaUcacUUgaggccaagagUgcaaggcUgUagUgUgcacagc
    4452 cUUGAAUUCUUGGCCUUAAGUGAUccc
    860 UAGGAGCUCAACAGAUGCCUGU hsa-mir-2294 hsa-mir- 1154 UcagagUAGGAGCUCAACAGAUGCCUGUUgacUgaaUaa
    3139 UaaacaggUaUcgcaggagcUUUUgUUaUgU
    861 AGCUUUUGGGAAUUCAGGUAG hsa-mir-2295 hsa-mir- 1155 UgUccUcUUgaggUaccUgaaUUaccaaaagcUUUaUgUaUU
    3140 cUgaagUUaUUgaaaaUaagAGCUUUUGGGAAUUCAGGU
    AGUUcaggagUgacU
    862 GAGCUUGGUCUGUAGCGGUU hsa-mir-2296 hsa-mir- 1156 UggaGAGCUUGGUCUGUAGCGGUUUccUUggggcaggUg
    4453 gggacUgcUccUUUgggaggaaggaggaggcccaggccgcgUcUU
    cagg
    863 GGAUCCGAGUCACGGCACCA hsa-mir-2297 hsa-mir- 1157 ccGGAUCCGAGUCACGGCACCAaaUUUcaUgcgUgUccgU
    4454 gUgaagagaccacca
    864 CAAAAGUGAUCGUGGUUUUUG hsa-mir-2298 hsa-mir- 1158 gUggUgCAAAAGUGAUCGUGGUUUUUGcaaUUUUUUaa
    548t UgacaaaaaccacaaUUacUUUUgcaccaa
    865 AGGGUGUGUGUGUUUUU hsa-mir-2299 hsa-mir- 1159 agaAGGGUGUGUGUGUUUUUccUgagaaUaagagaaggaa
    4455 ggacagccaaaUUcUUca
    866 CCUGGUGGCUUCCUUUU hsa-mir-2300 hsa-mir- 1160 aUgaaCCUGGUGGCUUCCUUUUcUgggaggaagUUagggU
    4456 Uca
    867 UCACAAGGUAUUGACUGGCGUA hsa-mir-2301 hsa-mir- 1161 ggagUacUccagUcaaUaccgUgUgagUUagaaaagcUcaaUU
    4457 CACAAGGUAUUGACUGGCGUAUUca
    868 AGAGGUAGGUGUGGAAGAA hsa-mir-2302 hsa-mir- 1162 gagcgcacAGAGGUAGGUGUGGAAGAAagUgaaacacUaU
    4458 UUUaggUUUUagUUacacUcUgcUgUggUgUgcUg
    869 CCAGGAGGCGGAGGAGGUGGAG hsa-mir-2303 hsa-mir- 1163 acCCAGGAGGCGGAGGAGGUGGAGgUUgcagUgagccaag
    4459 aUcgUggcacUgacUccagccUgggg
    870 GUGGAGGACUGAGAAGGUGAG hsa-mir-2304 pending 1164 aUgaUGUGGAGGACUGAGAAGGUGAGgcagUUUUgcccc
    gUgcUgccUUccaccggUUaagaccUccaaaaUcga
    871 ACUGACAGGAGAGCAUUUUGA hsa-mir-2305 hsa-mir- 1165 ggacaaaaUUaaaaUgcUcUUcUgUcaUUgUaaUagUUcaUa
    3660 UgggcACUGACAGGAGAGCAUUUUGAcUUUgUca
    872 AGCGCGGGCUGAGCGCUGCCAG hsa-mir-2306 hsa-mir- 1166 ggUUcacUggUcgUgcUUccUgcgggcUgAGCGCGGGCUGA
    2277 GCGCUGCCAGUcagcg
    873 AAGCUCGGGCGCUCCGGCUGU hsa-mir-2307 pending 1167 gcUcagUcagcUgggccgccUcagcUcUcggagUaggAAGCUCG
    GGCGCUCCGGCUGUaaggagcc
    874 AUAGUGGUUGUGAAUUUACCUU hsa-mir-2308 hsa-mir- 1168 gUUUUUUgcccAUAGUGGUUGUGAAUUUACCUUcUccU
    4460 cUUUgcagUgaUaaaggaggUaaaUUcacaaccacUgUgggcag
    aaac
    875 GAUUGAGACUAGUAGGGCUAGGC hsa-mir-2309 hsa-mir- 1169 gagUaggcUUaggUUaUgUacgUagUcUaggccaUacgUgUU
    4461 ggaGAUUGAGACUAGUAGGGCUAGGCcUacUg
    876 CUACCCCAGGAUGCCAGCAUAG hsa-mir-2310 pending 1171 aUagcUggUUggcaUUcUggcccUggUUcaUgccaacUcUUg
    UgUUgaCUACCCCAGGAUGCCAGCAUAGUUgc
    877 ACUGGACUUGGUGUCAGAUGG hsa-mir-2311 hsa-mir- 1171 acaggaacACUGGACUUGGUGUCAGAUGGgaUgagcccUg
    378h gcUcUgUUUccUagcagcaaUcUgaUcUUgagcUagUcacUgg
    878 GACAAUGAUGAGAAGACCUGAG hsa-mir-2312 pending 1172 gggGACAAUGAUGAGAAGACCUGAGgaUUUgcagccccca
    gcccUgggUUcaagUcccagcUcUaccccUUcUUggcccc
    879 ACCGCUCGAUCUUGGGACC hsa-mir-2313 pending 1173 gUUUcACCGCUCGAUCUUGGGACCcaccgcUgcccUcagcU
    ccgagUccagggcgaggUaagggcUggagUcgggcagga
    880 UAGUGGAUGAUGGAGACUCGGU hsa-mir-2314 hsa-mir- 1174 aUUgaggcacUgggUAGUGGAUGAUGGAGACUCGGUacc
    3691 cacUgcUgagggUggggaccaagUcUgcgUcaUccUcUccUcag
    UgccUcaaa
    881 CUCGGGAGCGUUAGAGAUGGA hsa-mir-2315 pending 1175 gUCUCGGGAGCGUUAGAGAUGGAgacUaacgUcUUccaa
    gggagaUUgcgUcUccacUUUcacccUggUacUgagag
    882 GGCUGGAGCGAGUGCAGUGGUG hsa-mir-2316 hsa-mir- 1176 UgcccaGGCUGGAGCGAGUGCAGUGGUGcagUcagUccU
    3135b agcUcacUgcagccUcgaacUccUgggcU
    883 UCAGGUGUGGAAACUGAGGCAG hsa-mir-2317 hsa-mir- 1177 UUUUCAGGUGUGGAAACUGAGGCAGgaggcagUgaagUa
    3934 acUUgcUcaggUUgcacagcUgggaagU
    884 UGACACGGAGGGUGGCUUGGGAA hsa-mir-2318 hsa-mir- 1178 cUUcccagcUgcccUaagUcaggagUggcUUUccUGACACGG
    4462 AGGGUGGCUUGGGAAa
    885 GAAGAUGGUGCUGUGCUGAGGA hsa-mir-2319 pending 1179 ggUGAAGAUGGUGCUGUGCUGAGGAaaggggaUgcagagc
    ccUgcccagcaccaccaccUccUaUg
    886 AAAGACUGCAAUUACUUUUGCG hsa-mir-2320 hsa-mir- 1180 aUggUgcaaaagUaaUgUggUUUUUUUcUUUacUUUUaaU
    548u ggcAAAGACUGCAAUUACUUUUGCGcca
    887 GAGACUGGGGUGGGGCC hsa-mir-2321 hsa-mir- 1181 aaUagaUUaUUggUcaccaccUccagUUUcUgaaUUUgUGA
    4463 GACUGGGGUGGGGCCUgagaaUUUgc
    888 AAGGUUUGGAUAGAUGCAAUA hsa-mir-2322 hsa-mir- 1182 ggaaccUUagUAAGGUUUGGAUAGAUGCAAUAaagUaUg
    4464 UccacagcUgaaaggacaUacUUUaUUgcaUgUaUccaaaccU
    UacUaaUUca
    889 AAAGGUAAUUGCAGUUUUUCCC hsa-mir-2323 hsa-mir- 1183 gUaUUaggUUggUgcAAAGGUAAUUGCAGUUUUUCCCa
    548ai UUUaaaaUaUggaaaaaaaaaUcacaaUUacUUUUgcaUcaa
    ccUaaUaa
    890 AGGGGACCAAAGAGAUAUAUAG hsa-mir-2324 hsa-mir- 1184 gaaacUacacUUUaAGGGGACCAAAGAGAUAUAUAGaUa
    3144 UcagcUaccUaUaUaccUgUUcggUcUcUUUaaagUgUagU
    UUa
    891 UAAAAACUGCAAUUACUUUUA hsa-mir-2325- hsa-mir- 1185 aUUggUgUaaaagUaaUUgcaggUUaUgccaUUaaaagUaaU
    1 548aj-1 ggUAAAAACUGCAAUUACUUUUAcacUaac
    892 UAAAAACUGCAAUUACUUUUA hsa-mir-2325- hsa-mir- 1186 aaggUaUUaggUUggUgcaaaagUaaUUgcagUUUUUgcUa
    2 548aj-2 UUacUUUUaaUggUAAAAACUGCAAUUACUUUUAcacca
    accUaaUaUUUa
    893 CUCAAGUAGUCUGACCAGGGGA hsa-mir-2326 hsa-mir- 1187 caUgUgUccccUggcacgcUaUUUgaggUUUacUaUggaacC
    4465 UCAAGUAGUCUGACCAGGGGAcacaUga
    894 UCUGGCUGAGGAGGAAGUGGAG hsa-mir-2327- pending 1188 gcUcUagUagccacagccaUccccUagagggaUCUGGCUGAGG
    1 AGGAAGUGGAGg
    895 UCUGGCUGAGGAGGAAGUGGAG hsa-mir-2327- pending 1189 ccgccUcagUggcUUccUccacagccaccUccggagggaUCUGGC
    2 UGAGGAGGAAGUGGAGgUgUcacUgg
    896 GGCGACAAAACGAGACCCUGU hsa-mir-2328 hsa-mir- 1190 cUgGGCGACAAAACGAGACCCUGUcUUUUUUUUUUUc
    1273c UgagacagagUcUcgUUcUgUUgcccaa
    897 GGGUGCGGGCCGGCGGGG hsa-mir-2329 hsa-mir- 1191 acgcGGGUGCGGGCCGGCGGGGUagaagccacccggcccggc
    4466 ccggcccggcga
    898 CCUGCUGGUCAGGAGUGGAUAC hsa-mir-2330 hsa-mir- 1192 gccaUUCCUGCUGGUCAGGAGUGGAUACUggagcaaUag
    3692 aUacagUUccacacUgacacUgcagaagUgga
    899 CAUGCUAGGAUAGAAAGAAUGG hsa-mir-2331 hsa-mir- 1193 aUUUUcUUUgcUaagUcccUUcUUUcUaUccUagUaUaac
    3146 UUgaagaaUUcaaaUagUCAUGCUAGGAUAGAAAGAAUG
    GgacUUggccagggaagaa
    900 AAUGUGGAAGUGGUCUGAGGCA hsa-mir-2332 pending 1194 gaaUagaaagAAUGUGGAAGUGGUCUGAGGCAUaUagag
    UaUaUgccaagaacacUaccaUa
    901 GCAAAGUGAUGAGUAAUACUGG hsa-mir-2333 hsa-mir- 1195 acagUaacUUUUaUUcUcaUUUUccUUUUcUcUaccUUgU
    3609 agagaaGCAAAGUGAUGAGUAAUACUGGcUgg
    902 UGGCGGCGGUAGUUAUGGGCUU hsa-mir-2334 hsa-mir- 1196 UggUGGCGGCGGUAGUUAUGGGCUUcUcUUUcUcacca
    4467 gcagccccUgggccgccgccUcccU
    903 AGAGCAGAAGGAUGAGAU hsa-mir-2335 hsa-mir- 1197 agUcUUcUccUggggcUUUggUggcUaUggUUgacUgggccac
    4468 UcAGAGCAGAAGGAUGAGAUg
    904 UGGAAUGGCCUGAAGGUGGA hsa-mir-2336 pending 1198 ccUggcagcccUcUggccUagUUcccaccacacaUgaggUggUG
    GAAUGGCCUGAAGGUGGAacaga
    905 GCUCCCUCUAGGGUCGCUCGGA hsa-mir-2337 hsa-mir- 1199 ccgacgcggagagcggcUcUaggUgggUUUggcggcggcgaggaca
    4469 ccgccGCUCCCUCUAGGGUCGCUCGGAgcgUga
    906 UGGCAAACGUGGAAGCCGAGA hsa-mir-2338 hsa-mir- 1200 cgagccUcUUUcggcUUUccagUUUgUcUcggUccUUUggaa
    4470 cgUGGCAAACGUGGAAGCCGAGAgggcUcU
    907 UUUGUAUGGAUAUGUGUGUGUA hsa-mir-2339 hsa-mir- 1201 aUaUacaUacaUgUacacacacaUgUcaUccacacacaUacaUa
    3149 UaUaUaUgUUUGUAUGGAUAUGUGUGUGUAUgUgUg
    UgUaUac
    908 UGAGGAGAUCGUCGAGGUUGGC hsa-mir-2340 hsa-mir- 1202 aaagcaggccaaccUcgaggaUcUccccagccUUggcgUUcaggU
    3150b gcUGAGGAGAUCGUCGAGGUUGGCcUgcUUc
    909 UGGGAACUUAGUAGAGGUUUAA hsa-mir-2341 hsa-mir- 1203 ccaaaUUUaaaacUUaaaccUcUacUaagUUUccaUgaaaaga
    4471 acccaUGGGAACUUAGUAGAGGUUUAAgUUUUaaaUUU
    ga
    910 GGUGGGGGGUGUUGUUUU hsa-mir-2342- hsa-mir- 1204 UggcagacccUUgcUcUcUcacUcUcccUaaUggggcUgaagac
    1 4472-1 agcUcaggggcagGGUGGGGGGUGUUGUUUUUgUUU
    911 GGUGGGGGGUGUUGUUUU hsa-mir-2342- hsa-mir- 1205 UggUgggGGUGGGGGGUGUUGUUUUUgUUUUUgagaca
    2 4472-2 gagUcUUgcUccgUcgcccaggccggagU
    912 CUAGUGCUCUCCGUUACAAGUA hsa-mir-2343 hsa-mir- 1206 aaggaacaggggacacUUgUaaUggagaacacUaagcUaUggac
    4473 UgcUaUggacUgCUAGUGCUCUCCGUUACAAGUAUcccc
    UgUUaccU
    913 CACUUGUAAUGGAGAACACUAA hsa-mir-2344 pending 1207 aaaggaacaggggaCACUUGUAAUGGAGAACACUAAgcUa
    UggacUgcUaUggacUgcUagUgcUcUccgUUacaagUaUccc
    cUgUUaccUUg
    914 UUGUGGCUGGUCAUGAGGCUAA hsa-mir-2345 hsa-mir- 1208 UUgccUaccUUgUUagUcUcaUgaUcagacacaaaUaUggcUc
    4474 UUUGUGGCUGGUCAUGAGGCUAAcaaggUaggcac
    915 CCCUGGGGUUCUGAGGACAUG hsa-mir-2346 pending 1209 aUgcUgCCCUGGGGUUCUGAGGACAUGcUcUgacUcccc
    UgaUgUccUcUgUUccUcaggUgcUgggcga
    916 CAAGGGACCAAGCAUUCAUUAU hsa-mir-2347 hsa-mir- 1210 aUcUcaaUgagUgUgUggUUcUaaaUgacUcaUagUCAAGG
    4475 GACCAAGCAUUCAUUAUgaa
    917 CAGGAAGGAUUUAGGGACAGGC hsa-mir-2348 hsa-mir- 1211 aaaagccUgUcccUaagUcccUcccagccUUccagagUUggUgc
    4476 CAGGAAGGAUUUAGGGACAGGCUUUg
    918 CUAUUAAGGACAUUUGUGAUUC hsa-mir-2349 hsa-mir- 1212 UccUccUcccaUcaaUcacaaaUgUccUUaaUggcaUUUaagg
    4477a aUUgCUAUUAAGGACAUUUGUGAUUCacgggaggaggU
    919 AUUAAGGACAUUUGUGAUUGAU hsa-mir-2350 hsa-mir- 1213 accUccUcccgUgaaUcacaaaUgUccUUaaUagcaaUccUUaa
    4477b aUgccAUUAAGGACAUUUGUGAUUGAUgggaggagga
    920 AAAAGGCAUAAAACCAAGACA hsa-mir-2351- hsa-mir- 1214 cUUUUUUUgUUgcUUgUcUUggUUUUaUgccUUUUaUg
    1 3910-2 UgccUUgaUaUAAAAGGCAUAAAACCAAGACAagcaacag
    aaaaac
    921 AAAAGGCAUAAAACCAAGACA hsa-mir-2351- hsa-mir- 1215 cUgUcagUUUUUcUgUUgcUUgUcUUggUUUUaUgccUU
    2 3910-1 UUaUaUcaaggcacaUAAAAGGCAUAAAACCAAGACAagc
    aacaa
    922 GAGGCUGAGCUGAGGAG hsa-mir-2352 hsa-mir- 1216 ggccGAGGCUGAGCUGAGGAGccUccaaaccUgUagacagg
    4478 gUcaUgcagUacUaggggcgagccUcaUccccUgcagcccUggcc
    923 CUGGGAGGUGUGAUAUUGUGGU hsa-mir-2353 hsa-mir- 1217 gggaggUgUgaUaUcgUggUUccUgggaggUgUgaUaUcgUg
    3689c gUUcCUGGGAGGUGUGAUAUUGUGGUUccU
    924 UAAAAACUGCAAUUACUUUC hsa-mir-2354- hsa-mir- 1218 aUgccaaaUaUUaggUUggcacaaaagUaaUUgUggcUUUUg
    1 548x-2 ccaUUaaaagUaaUggUAAAAACUGCAAUUACUUUCgUgc
    caaccUaaUaUUUgUgUg
    925 UAAAAACUGCAAUUACUUUC hsa-mir-2354- hsa-mir- 1219 agUgcaaaagUaaUUgcagUUUUUgcgUUacUUUcaaUcgU
    2 548x-1 AAAAACUGCAAUUACUUUCacacc
    926 UGUGAUAUCAUGGUUCCUGGGA hsa-mir-2355- hsa-mir- 1220 gcUcccUgggaggUGUGAUAUCAUGGUUCCUGGGAggUg
    1 3689a UgaUccUgUgcUUccUgggaggUgUgaUaUcgUggUUccUgg
    gagg
    927 GGGAGGUGUGAUCUCACACUCG has-mir-2356- hsa-mir- 1221 UGGGAGGUGUGAUCUCACACUCGcUgggaggUgUgcUaU
    1 3689d-1 cgUcUUccccgggaggUgUgaUccUgUUcUUccUg
    928 CUGGGAGGUGUGAUAUUGUGGU mir-2355-2* has-mir- 1222 gggaggUGUGAUAUCAUGGUUCCUGGGAggUgUgaUccc
    3689b-1 gUgcUUcCUGGGAGGUGUGAUAUUGUGGUUccU
    929 UGUGAUAUCAUGGUUCCUGGGA hsa-mir-2355- hsa-mir- 1223 gggaggUGUGAUAUCAUGGUUCCUGGGAggUgUgaUccc
    2 3689b-1 gUgcUUcCUGGGAGGUGUGAUAUUGUGGUUccU
    930 GGGAGGUGUGAUCUCACACUCG has-mir-2356- hsa-mir- 1224 acUGGGAGGUGUGAUCUCACACUCGcUgggaggUgUgcU
    2 3689d-2 aUcgUcUUcccUgggaggUgUgaUccUgUUcUUccUgagcg
    931 UGUGAUAUCAUGGUUCCUGGGA hsa-mir-2355- has-mir- 1225 gggaggUGUGAUAUCAUGGUUCCUGGGAggUaUgaUaUc
    3 3689b-2 gUggUUccUgggaggUgUgaUcccgUgcUcccU
    932 UGUGAUAUCGUGCUUCCUGGGA hsa-mir-2355b hsa-mir- 1226 aggUGUGAUAUCGUGCUUCCUGGGAcgUgUgaUgcUgUg
    3689f cUUccUgggaggUgUgaUcccacacUc
    933 CGCGCGGCCGUGCUCGGAGCAG hsa-mir-2356 hsa-mir- 1227 gaaaccaagUccgagcgUggcUggcgcgggaaagUUcgggaacgC
    4479 GCGCGGCCGUGCUCGGAGCAGcgcca
    934 CCAGGCUCUGCAGUGGGAACU hsa-mir-2357a hsa-mir- 1228 ccUgUUccgggcaUcaccUcccacUgcagagccUggggagccggac
    3155a agcUcccUUcCCAGGCUCUGCAGUGGGAACUgaUgccUgg
    aacagU
    935 CCAGGCUCUGCAGUGGGA hsa-mir-2357b hsa-mir- 1229 ccacUgcagagccUgggaagggagcUgUccggcUccCCAGGCUC
    3155b UGCAGUGGGAgU
    936 AAAAGUAACUGCGGUUUUUGA hsa-mir-2358 hsa-mir- 1230 gUgcAAAAGUAACUGCGGUUUUUGAgaagUaaUUgaaaa
    548ak ccgcaaUUacUUUUgcag
    937 AGCCAAGUGGAAGUUACUUUA hsa-mir-2359 hsa-mir- 1231 gcagaggUgagUUgaccUccacagggccacccagggagUaagUAG
    4480 CCAAGUGGAAGUUACUUUAccUcUgU
    938 GGAGUGGGCUGGUGGUU hsa-mir-2360 hsa-mir- 1232 GGAGUGGGCUGGUGGUUUUUUaagaggaagggagaccUa
    4481 agcUagcacaUgagcacgcUc
    939 GAGCGAUCCGAGGGACUG hsa-mir-2361 pending 1233 cggcUUcccgcggUccccggUgcUgaggagaGAGCGAUCCGAG
    GGACUGcgccgcc
    940 AAGGGCUUCCUCUCUGCAGGAC hsa-mir-2362- hsa-mir- 1234 acaUUaUUcaggccggUccUgcagagaggaagcccUUccaaUacc
    1 3158-2 UgUaagcagAAGGGCUUCCUCUCUGCAGGACcggccUgaa
    UaaUga
    941 AAGGGCUUCCUCUCUGCAGGAC hsa-mir-2362- hsa-mir- 1235 ggaUcaUUaUUcaggccggUccUgcagagaggaagcccUUcUgc
    2 3158-1 UUacaggUaUUggAAGGGCUUCCUCUCUGCAGGACcggcc
    UgaaUaaUgUaaUca
    942 AACCCAGUGGGCUAUGGAAAUG hsa-mir-2363 hsa-mir- 1236 agUgagcAACCCAGUGGGCUAUGGAAAUGUgUggaagaU
    4482 ggcaUUUcUaUUUcUcagUggggcUcUUacc
    943 GGGGUGGUCUGUUGUUG hsa-mir-2364 hsa-mir- 1237 aaaaaacaacaUacUUagUgcaUacccaUaUaaUaUUaGGGG
    4483 UGGUCUGUUGUUGUUUUUcU
    944 AAAAGGCGGGAGAAGCCCCA hsa-mir-2365 hsa-mir- 1238 gggUUUccUcUgccUUUUUUUccaaUgaaaaUaacgaaaccU
    4484 gUUaUUUcccaUUgagggggaAAAAGGCGGGAGAAGCCCC
    A
    945 UGGCUGUUGGAGGGGGCAGGCU hsa-mir-2366 pending 1239 ggagccagcccUccUcccgcacccaaacUUggagcacUUgaccUU
    UGGCUGUUGGAGGGGGCAGGCUcg
    946 UAACGGCCGCGGUACCCUAA hsa-mir-2367 hsa-mir- 1240 agaggcaccgccUgcccagUgacaUgcgUUUAACGGCCGCGG
    4485 UACCCUAAcUgUgca
    947 UAGGAUUACAAGUGUCGGCCAC hsa-mir-2368 hsa-mir- 1241 ccUAGGAUUACAAGUGUCGGCCACgggcUgggcacagUggc
    3159 UcacgccUgUaaUcccagc
    948 GCUGGGCGAGGCUGGCA hsa-mir-2369 hsa-mir- 1242 gcaUGCUGGGCGAGGCUGGCAUcUagcacaggcggUagaUg
    4486 cUUgcUcUUgccaUUgcaaUga
    949 AGAGCUGGCUGAAGGGCAG hsa-mir-2370 hsa-mir- 1243 acUgUccUUcagccAGAGCUGGCUGAAGGGCAGaagggaac
    4487 UgUccUUcagccagagcUggcUgaagggcaga
    950 AGGGGGCGGGCUCCGGCG hsa-mir-2371 hsa-mir- 1244 ggUAGGGGGCGGGCUCCGGCGcUgggaccccacUagggUgg
    4488 cgccUUggccccgccccgccc
    951 GCCGAGAGUCGUCGGGGUU hsa-mir-2372 pending 1245 UcGCCGAGAGUCGUCGGGGUUUccUgcUUcaacagUgcU
    Uggacggaacccggcgc
    952 UGGGGCUAGUGAUGCAGGACG hsa-mir-2373 hsa-mir- 1246 gggggUGGGGCUAGUGAUGCAGGACGcUggggacUggaga
    4489 agUccUgccUgacccUgUccca
    953 UGUGACUUUAAGGGAAAUGGCG hsa-mir-2374 hsa-mir- 1247 UggaaacUGUGACUUUAAGGGAAAUGGCGcacagcagacc
    3164 cUgcaaUcaUgccgUUUUgcUUgaagUcgcagUUUccc
    954 UCUCAGGAGUAAAGACAGAGUU hsa-mir-2375 hsa-mir- 1248 aacUUgaaggUagggaacUcUgUcUUcacUcaUgagUaccUUc
    3664 caacacgagcUCUCAGGAGUAAAGACAGAGUUcccUaccU
    UcaaUgU
    955 AGGUGGAUGCAAUGUGACCUCA hsa-mir-2376 hsa-mir- 1249 caAGGUGGAUGCAAUGUGACCUCAacUcUUggUccUcUg
    3165 aggUcacaUUgUaUccaccUUa
    956 AACGGCAAUGACUUUUGUACCA hsa-mir-2377 hsa-mir- 1250 ggUcggUgcaaaagUaaUUgcUgUUUUUgccaUUaaaaaUaa
    548a1 UggcaUUaaaagUaaUggcaaaAACGGCAAUGACUUUUGU
    ACCAaUcUaaUaUcU
    957 UCUGGUAAGAGAUUUGGGCAUA hsa-mir-2378 hsa-mir- 1251 aUagUUUcUgcaaUgcUcaaaUcUcUggccaaagaccagaacU
    4490 UaaUggUcUCUGGUAAGAGAUUUGGGCAUAUUagaaac
    Uaa
    958 AAUGUGGACUGGUGUGACCAAA hsa-mir-2379- hsa-mir- 1252 acaUUUggUcacaccagUccacaUUaacgUggaccagacaaUaU
    1 4491 UAAUGUGGACUGGUGUGACCAAAa
    959 AAUGUGGACUGGUGUGACCAAA hsa-mir-2379- pending 1253 accUggacaUUUggUcacaccagUccacaUUaacgUggaccagac
    2 aaUaUUAAUGUGGACUGGUGUGACCAAAagUccaggc
    960 GGGGCUGGGCGCGCGCC hsa-mir-2380 hsa-mir- 1254 cUgcagcgUgcUUcUccaggccccgcgcgcggacagacacacgga
    4492 caagUcccgccaGGGGCUGGGCGCGCGCCagccgg
    961 AGAAGGCCUUUCCAUCUCUGU hsa-mir-2381 hsa-mir- 1255 ccagagaUgggaaggccUUccggUgaUUaUcacagccaUgccUU
    4493 UaccUccAGAAGGCCUUUCCAUCUCUGUc
    962 CCAGACUGUGGCUGACCAGAGG hsa-mir-2382 hsa-mir- 1256 agUUUUagUUacccUggUcaUcUgcagUcUgaaaaUacaaaa
    4494 UggaaaaUUCCAGACUGUGGCUGACCAGAGGUaacUgaa
    acc
    963 AGGAGAAGCAGGAGCUGU hsa-mir-2383 pending 1257 cUgAGGAGAAGCAGGAGCUGUcUUggUacaUUcaggUcac
    Ug
    964 AAUGUAAACAGGCUUUUUGCU hsa-mir-2384 hsa-mir- 1258 aagaAAUGUAAACAGGCUUUUUGCUcagUggagUUaUUU
    4495 UgagcaaaaagcUUaUUUacaUUUcUg
    965 GAGGAAACUGAAGCUGAGAGGG hsa-mir-2385 hsa-mir- 1259 ACAUCAGCUCAUAUAAUCCUCGAAGCUGCCUUUAGAA
    4496 AUGAGGAAACUGAAGCUGAGAGGG
    966 CUCCGGGACGGCUGGGC hsa-mir-2386 hsa-mir- 1260 acCUCCGGGACGGCUGGGCgccggcggccgggagaUccgcgcU
    4497 UccUgaaUcccggccggcccgcccggcgcccgUccgcccgcgggUc
    967 UGGGCUGGCAGGGCAAGUGCUG hsa-mir-2387 hsa-mir- 1261 agggcUGGGCUGGCAGGGCAAGUGCUGcagaUcUUUgUc
    4498 UaagcagccccUgccUUggaUcUccca
    968 GAGGCUGAAGGAAGAUGG hsa-mir-2388 hsa-mir- 1262 cUcaggcUcagUggUgcaUgcUUaUagUcccagccacUcUgGA
    4419b GGCUGAAGGAAGAUGGcUUgagccU
    969 AAGACUGAGAGGAGGGA hsa-mir-2389 hsa-mir- 1263 AAGACUGAGAGGAGGGAacUggUgagUUgUacaUagaaa
    4499 UgcUUUcUaacUccUUgUcUcagUcUgUUU
    970 UGAGGUAGUAGUUUCUU hsa-mir-2390 hsa-mir- 1264 caggagagaaagUacUgcccagaagcUaaagUgUagaUcaaacgc
    4500 aUaaUggcUGAGGUAGUAGUUUCUUgaacUU
    971 CGGCUGGGAGCCGAGGCGUCGG hsa-mir-2391 pending 1265 ggCGGCUGGGAGCCGAGGCGUCGGUgcagaccUggagacg
    ggcaUgggggggcUgcggcUgcUggcUgUg
    972 UAUGUGACCUCGGAUGAAUCA hsa-mir-2392 hsa-mir- 1266 UAUGUGACCUCGGAUGAAUCAcUgaaaUaUgUcUgagcU
    4501 UcUgUUUcaUcagaUgUcacaUUUU
    agccUUUagcaagUUgUaaUcUUUUUgcUgaUggagggUcU
    973 GCUGAUGAUGAUGGUGCUGAAG hsa-mir-2393 hsa-mir- 1267 UgccUccaUggggaUgGCUGAUGAUGAUGGUGCUGAAGg
    4502 c
    974 AGAUGUAUGGAAUCUGUAUAU hsa-mir-2394 hsa-mir- 1268 gAGAUGUAUGGAAUCUGUAUAUaUcUaUaUaUaUgUgU
    3171 aUaUaUagaUUccaUaaaUcUa
    975 UUUAAGCAGGAAAUAGAAUUUA hsa-mir-2395 hsa-mir- 1269 acaaUgUagaUaUUUAAGCAGGAAAUAGAAUUUAcaUaU
    4503 aaaUUUcUaUUUgUUUcUaUUUccUgcUUaaaUaUcUaca
    UUgc
    976 UGUGACAAUAGAGAUGAACAUG hsa-mir-2396 hsa-mir- 1270 cUaagaUaaUgUccUccaggUUcaUcUcUgUUgUcaUUUgU
    4504 ggcaUggaccaUUUGUGACAAUAGAGAUGAACAUGgagga
    UaUUaUcUUaa
    977 AGGCUGGGCUGGGACGGA hsa-mir-2397 hsa-mir- 1271 ggAGGCUGGGCUGGGACGGAcacccggccUccacUUUcUg
    4505 UggcaggUaccUccUccaUgUcggcccgccUUg
    978 AAAUGGGUGGUCUGAGGCAA hsa-mir-2398 hsa-mir- 1272 UggccUcUgccaUcagaccaUcUgggUUcaagUUUggcUccaU
    4506 cUUUaUgAAAUGGGUGGUCUGAGGCAAgUggUcU
    979 UAGGAUGGGGGUGAGAGGUG hsa-mir-2399 hsa-mir- 1273 aUggUcccUcccaaUccagccaUUccUcagaccaggUggcUcccg
    2392 agccaccccaggcUgUAGGAUGGGGGUGAGAGGUGcUag
    980 CUGGGUUGGGCUGGGCUGGG hsa-mir-2400 hsa-mir- 1274 UcUgggcUgagccgagcUgggUUaagccgagCUGGGUUGGGC
    4507 UGGGCUGGGU
    981 AAGGGACUGGAGUGGAUUGGGU hsa-mir-2401 pending 1275 ggAAGGGACUGGAGUGGAUUGGGUacaUcUaUUaUagU
    gggagcaccUacUacaacccgUcccUcaagagUcgagUcacc
    982 AAGGGGCUGGAGUGGAUUGGGG hsa-mir-2402 pending 1276 cUggUgaaUcUgggUccgccagcccccagggAAGGGGCUGGA
    GUGGAUUGGGGaaaUccaU
    983 GCGGGGCUGGGCGCGCG hsa-mir-2403 hsa-mir- 1277 aggacccaGCGGGGCUGGGCGCGCGgagcagcgcUgggUgca
    4508 gcgccUgcgccggcagcUgcaagggccg
    984 ACUAAAGGAUAUAGAAGGUUUU hsa-mir-2404- hsa-mir- 1278 cUUUaaUacUaUcUcaaACUAAAGGAUAUAGAAGGUUU
    1 4509-1 UcccUUUcUcUUgcccUgaaaccUUcUgUaUccUUUaUUUU
    gagaUagUaUUagaa
    985 ACUAAAGGAUAUAGAAGGUUUU hsa-mir-2404- hsa-mir- 1279 cUUUaaUacUaUcUcaaACUAAAGGAUAUAGAAGGUUU
    2 4509-2 UcccUUUcUcUUgcccUgaaaccUUcUgUaUccUUUaUUUU
    gagaUagUaUUagaa
    986 ACUAAAGGAUAUAGAAGGUUUU hsa-mir-2404- hsa-mir- 1280 cUUUaaUacUaUcUcaaACUAAAGGAUAUAGAAGGUUU
    3 4509-3 UcccUUUcUcUUgcccUgaaaccUUcUgUaUccUUUaUUUU
    gagaUagUaUUagaa
    987 AAGCAAUACUGUUACCUGAAAU hsa-mir-2405 hsa-mir- 1281 cUcaaagAAGCAAUACUGUUACCUGAAAUaggcUgcgaaga
    3942 UaacagUaUUUcagaUaacagUaUUacaUcUUUgaa
    988 UGAGGGAGUAGGAUGUAUGGUU hsa-mir-2406 hsa-mir- 1282 gUgUaUgUGAGGGAGUAGGAUGUAUGGUUgUUagaUa
    4510 gacaacUacaaUcUUUUcUcacaacagacag
    989 GAAGAACUGUUGCAUUUGCCCU hsa-mir-2407 hsa-mir- 1283 aaaaaaaagggaaaGAAGAACUGUUGCAUUUGCCCUgcac
    4511 UcagUUUgcacagggUaaaUgcaaUagUUcUUcUUUcccUU
    UUUUUa
    990 CAGGGCCUCACUGUAUCGCCCA hsa-mir-2408 hsa-mir- 1284 cUcagcccgggcaaUaUagUgagaccUcgUcUcUacaaaaaaUU
    4512 gagaCAGGGCCUCACUGUAUCGCCCAggcUgga
    aUUcUaggUggggAGACUGACGGCUGGAGGCCCAUaagc
    991 AGACUGACGGCUGGAGGCCCAU hsa-mir-2409 hsa-mir- 1285 UgUcUaaaacUUcggcccccagaUUUcUggUcUccccacUUcag
    4513 aac
    992 ACAGGCAGGAUUGGGGAA hsa-mir-2410 hsa-mir- 1286 gUUgagACAGGCAGGAUUGGGGAAacaUcUUUUaccUcg
    4514 UcUcUUgccUgUUUUaga
    993 AGGACUGGACUCCCGGCAGCCC hsa-mir-2411 hsa-mir- 1287 gcgggaggUgUaacAGGACUGGACUCCCGGCAGCCCcaggg
    4515 caggggcgUggggagcUggUccUagcUcagcgcUcccgga
    994 UAGUGAGUUAGAGAUGCAGAGC hsa-mir-2412 hsa-mir- 1288 agcgUUaccUggUAGUGAGUUAGAGAUGCAGAGCccUgg
    3174 gcUccUcagcaaaccUacUggaUcUgca
    995 ACUGGCCUGGGACUACCGGGGG hsa-mir-2413 hsa-mir- 1289 UcUgcagcUcccggcagccUcgggccacacUcccgggaUccccag
    3176 ggACUGGCCUGGGACUACCGGGGGUggcggc
    996 GGGAGAAGGGUCGGGGC hsa-mir-2414 hsa-mir- 1290 aGGGAGAAGGGUCGGGGCagggagggcagggcaggcUcUgg
    4516 ggUggggggUcUgUgagUcagccacggcUcUgcccacgUcUcccc
    997 UGGGGCGGAGCUUCCGGAGGCC hsa-mir-2415- hsa-mir- 1291 agcUUccagacgcUccgccccacgUcgcaUgcgccccgggaacgc
    1 3180-1 gUGGGGCGGAGCUUCCGGAGGCCcc
    998 UGGGGCGGAGCUUCCGGAGGCC hsa-mir-2415- hsa-mir- 1292 agcUUccagacgcUccgccccacgUcgcaUgcgccccgggaacgc
    2 3180-2 gUGGGGCGGAGCUUCCGGAGGCCcc
    999 UGGGGCGGAGCUUCCGGAGGCC hsa-mir-2415- hsa-mir- 1293 agcUUccagacgcUccgccccacgUcgcaUgcgccccgggaacgc
    3 3180-3 gUGGGGCGGAGCUUCCGGAGGCCcc
    1000 UGGGGCGGAGCUUCCGGAGGCC hsa-mir-2415- hsa-mir- 1294 agcUUccagacgcUccgccccacgUcgcaUgcgccccgggaacgc
    4 3180-4 gUGGGGCGGAGCUUCCGGAGGCCcc
    1001 UGGGGCGGAGCUUCCGGAGGCC hsa-mir-2415- hsa-mir- 1295 agcUUccagacgcUccgccccacgUcgcaUgcgccccgggaacgc
    5 3180-5 gUGGGGCGGAGCUUCCGGAGGCCcc
    1002 CUCGUGGGCUCUGGCCACGGC hsa-mir-2416 hsa-mir- 1296 UggagggcaUUaggcagUggccagagcccUgcagUgcUgggcaUg
    3677 ggcUUCUCGUGGGCUCUGGCCACGGCccUgagcUccUcc
    1003 AGAAGGGGUGAAAUUUAAACGU hsa-mir-2417- hsa-mir- 1297 gccaggaUcacagacgUUUaaaUUacacUccUUcUgcUgUgcc
    1 3179-1 UUacagcagUAGAAGGGGUGAAAUUUAAACGUcUgUga
    UccUggg
    1004 AGAAGGGGUGAAAUUUAAACGU hsa-mir-2417- hsa-mir- 1298 gaUcacagacgUUUaaaUUacacUccUUcUgcUgUgccUUaca
    2 3179-2 gcagUAGAAGGGGUGAAAUUUAAACGUcUgUgaUccUgg
    g
    1005 AGAAGGGGUGAAAUUUAAACGU hsa-mir-2417- hsa-mir- 1299 gccaggaUcacagacgUUUaaaUUacacUccUUcUgcUgUgcc
    3 3179-3 UUacagcagUAGAAGGGGUGAAAUUUAAACGUcUgUga
    UccUgg
    1006 AAAUAUGAUGAAACUCACAGCUG hsa-mir-2418 hsa-mir- 1300 aggUAAAUAUGAUGAAACUCACAGCUGAGgagcUUagca
    AG 4517 agUagcUaaggccagagcUUgUgUUUgggUggUgUggcUg
    1007 GCUCAGGGAUGAUAACUGUGCUG hsa-mir-2419 hsa-mir- 1301 UgggggaaaagUgcUgggaUUgaUUagUgaUgUcUgcUgggga
    AGA 4518 accgggGCUCAGGGAUGAUAACUGUGCUGAGAagcccccU
    1008 CAGCAGUGCGCAGGGCUG hsa-mir-2420 hsa-mir- 1302 aaccUCAGCAGUGCGCAGGGCUGcacUgUcUccgUcUgcgg
    4519 ccUgcagUaagcgggUa
    1009 UUGGACAGAAAACACGCAGGAA hsa-mir-2421 hsa-mir- 1303 gUgUgccaccUgcgUgUUUUcUgUccaaaUcagaaaaggaUU
    4520 UGGACAGAAAACACGCAGGAAgaaggaa
    1010 GCUAAGGAAGUCCUGUGCUCAG hsa-mir-2422 hsa-mir- 1304 UcgGCUAAGGAAGUCCUGUGCUCAGUUUUgUagcaUca
    4521 aaacUaggaUUUcUcUUgUUac
    1011 CUGGACUGAGCCAUGCUACUGG hsa-mir-2423 hsa-mir- 1305 UgaggUUUCUGGACUGAGCCAUGCUACUGGcUUcUcUg
    1269b gUUcUccagcUUacagaUggcUUaUcaUgggaccUcU
    1012 UGACUCUGCCUGUAGGCCGGU hsa-mir-2424 hsa-mir- 1306 gcgggcgUUgccUgggggccUcgcagggggagaUccagcccaggcU
    4522 ggUUccgcUGACUCUGCCUGUAGGCCGGUggcgUcUUcU
    gg
    1013 GACCGAGAGGGCCUCGGCUGU hsa-mir-2425 hsa-mir- 1307 gcggggGACCGAGAGGGCCUCGGCUGUgUgaggacUagagg
    4523 cggccgaggcccgggccggUUcccccga
    1014 UAGAGGCUGGAAUAGAGAUUCU hsa-mir-2426 pending 1308 aUUUUAGAGGCUGGAAUAGAGAUUCUUgaggcUUggaa
    gagUaaggaUcccUUUaUcUgUccUcUaggag
    1015 UAGCCUUCAGAUCUUGGUGUUU hsa-mir-2427 hsa-mir- 1309 UggaUcUgaaggcUgccccUUUgcUcUcUggggUAGCCUUCA
    3614 GAUCUUGGUGUUUU
    1016 CCACUUGGAUCUGAAGGCUGCC hsa-mir-2427* has-mir- 1310 UgggCCACUUGGAUCUGAAGGCUGCCccUUUgcUcUcUg
    3614 gggUagccUUcagaUcUUggUgUUUU
    1017 AUAGCAGCAUGAACCUGUCUCA hsa-mir-2428 hsa-mir- 1311 gaacgAUAGCAGCAUGAACCUGUCUCAcUgcagaaUUaUU
    4524 UUgagacaggcUUaUgcUgcUaUccUUca
    1018 UGAGACAGGCUUAUGCUGCUAU hsa-mir-2428* has-mir- 1312 ggaacgaUagcagcaUgaaccUgUcUcacUgcagaaUUaUUUU
    4524 GAGACAGGCUUAUGCUGCUAUccUUca
    1019 GGGGGGAUGUGCAUGCUGGUU hsa-mir-2429 hsa-mir- 1313 gUcagaGGGGGGAUGUGCAUGCUGGUUggggUgggcUgc
    4525 cUgUggaccaaUcagcgUgcacUUccccacccUgaa
    1020 CAGGGAGGUGAAUGGUUCUGUC hsa-mir-2430 pending 1314 cUUagcUcccUggcUUcagcccUUUUUcCAGGGAGGUGAA
    UGGUUCUGUCUcgc
    1021 GCUGACAGCAGGGCUGGCCGCU hsa-mir-2431 hsa-mir- 1315 UgcggUgacaUcagggcccagUcccUgcUgUcaUgccccaggUga
    4526 cgUgcUggGCUGACAGCAGGGCUGGCCGCUaacgUcacUg
    Uc
    1022 UGGUCUGCAAAGAGAUGACUGU hsa-mir-2432 hsa-mir- 1316 ccagaagUGGUCUGCAAAGAGAUGACUGUgaaUccaagaU
    4527 ccacaUcagcUcUgUgcUgccUacaUcUga
    1023 UCAUUAUAUGUAUGAUCUGGAC hsa-mir-2433 hsa-mir- 1317 UaUUcUacUgagagUacagaUcUUUaUaUaUaUgaUcaUUa
    4528 UaUgUaUgaUgagaUCAUUAUAUGUAUGAUCUGGACacc
    cagUagaaUc
    1024 AUUGGACUGCUGAUGGCCCGU hsa-mir-2434 hsa-mir- 1318 aUgacaggccaUcagcagUccaaUgaagacaUgaagacccaaUgU
    4529 cUUcAUUGGACUGCUGAUGGCCCGUcacUggga
    1025 UUGGAGGGUGUGGAAGACAUC hsa-mir-2435 pending 1319 cUccacaUUGGAGGGUGUGGAAGACAUCUgggccaacUcU
    gaUcUcUUcaUcUaccccccaggacUggga
    1026 CCCAGCAGGACGGGAGCG hsa-mir-2436 hsa-mir- 1320 cgaccgcacccgcccgaagcUgggUcaaggagCCCAGCAGGACG
    4530 GGAGCGcggcgc
    1027 AUGGAGAAGGCUUCUGA hsa-mir-2437 hsa-mir- 1321 gccUaggagUccUUggUcagUggggacAUGGAGAAGGCUUC
    4531 UGAgga
    1028 AAAAGCUGGGUUGAGAA hsa-mir-2438 hsa-mir- 1322 gccUUcUcUUcccagUUcUUccUggagUcggggAAAAGCUG
    320e GGUUGAGAAggUgaaaaga
    1029 UGGAAGGUAGACGGCCAGAGAG hsa-mir-2439 hsa-mir- 1323 ggUcaccUgUcUggccagcUacgUccccacggcccUUgUcagUg
    3190 UGGAAGGUAGACGGCCAGAGAGgUgaccc
    1030 UCUGGGAGGUUGUAGCAGUGGA hsa-mir-2440 hsa-mir- 1324 aggaagggaUUCUGGGAGGUUGUAGCAGUGGAaaaagUU
    3192 cUUUUcUUccUcUgaUcgcccUcUcagcUcUUUccUUcUg
    1031 CCCCGGGGAGCCCGGCG hsa-mir-2441 hsa-mir- 1325 acagaCCCCGGGGAGCCCGGCGgUgaagcUccUggUaUccU
    4532 gggUgUcUga
    1032 UGGAAGGAGGUUGCCGGACGCU hsa-mir-2442 hsa-mir- 1326 UgagaaUgUGGAAGGAGGUUGCCGGACGCUgcUggcUgc
    4533 cUUccagcgUccacUUcccUUUcUcUcUcUcc
    1033 CAAGAACCUCAAUUACCUUUGC hsa-mir-2443 pending 1327 cggUUggUgcaaaggUaaUUgUggUUUcUgccaUUgaaagUa
    aaggCAAGAACCUCAAUUACCUUUGCagcgaccU
    1034 AAUCUGAGAAGGCGCACAAGGU hsa-mir-2444 has-mir- 1328 UcgagggAAUCUGAGAAGGCGCACAAGGUUUgUgUccaa
    3200 UacagUccacaccUUgcgcUacUcaggUcUgcUcgUg
    1035 CACCUUGCGCUACUCAGGUCUG hsa-mir-2444* hsa-mir- 1329 UcgagggaaUcUgagaaggcgcacaaggUUUgUgUccaaUacag
    3200 UccaCACCUUGCGCUACUCAGGUCUGcUcgU
    1036 GGAGGAACCUUGGAGCUUCGGC hsa-mir-2445 hsa-mir- 1330 ggcUgaagcUcUaaggUUccgccUgcgggcaggaagcGGAGGA
    3928 ACCUUGGAGCUUCGGCa
    1037 GGAUGGAGGAGGGGUCU hsa-mir-2446 hsa-mir- 1331 UgUgaaUgacccccUUccagagccaaaaUcaccagGGAUGGAG
    4534 GAGGGGUCUUgggUacU
    1038 ACUGGACUAGGAGUCAGAAGG hsa-mir-2447 hsa-mir- 1332 gggagcACUGGACUAGGAGUCAGAAGGUggagUUcUggg
    378i UgcUgUUUUcccacUcUUgggcccUgggcaUgUUcUg
    1039 GUGGACCUGGCUGGGAC hsa-mir-2448 hsa-mir- 1333 aacUgggUcccagUcUUcacagUUggUUUcUgacacGUGGAC
    4535 CUGGCUGGGACgaUgUg
    1040 ACCUGGACCCAGCGUAGACAAA hsa-mir-2449 hsa-mir- 1334 ccACCUGGACCCAGCGUAGACAAAgaggUgUUUcUacUcc
    3690 aUaUcUaccUggacccagUgU
    1041 CAAAAACUGCAGUUACUUUUGU hsa-mir-2450 hsa-mir- 1335 agUUggUgcaaaagUaaUUgcggUUUUUgccgUcgaaaaUaa
    548am UggCAAAAACUGCAGUUACUUUUGUaccaaUg
    1042 UUGGGCUGGGCUGGGUUGGG hsa-mir-2451 hsa-mir- 1336 UUUGGGCUGGGCUGGGUUGGGcagUUcUUcUgcUggac
    1587 UcaccUgUgaccagc
    1043 UGUGGUAGAUAUAUGCACGAU hsa-mir-2452 hsa-mir- 1337 aUgUgUggUagaUaUaUgcacUgUaUaUaaacaUaaUGUGG
    4536 UAGAUAUAUGCACGAUaUag
    1044 AGAAGGGAAAGAACAUCAA hsa-mir-2453 pending 1338 aUggUgUUUgccUccUUcaUccgcaaggcaUcUgaUgcccacga
    agUUaggaaggUccUUggggAGAAGGGAAAGAACAUCAAa
    1045 CUGUCCUAAGGUUGUUGAGUU hsa-mir-2454 hsa-mir- 1339 cgcaUgacUcUUcaaccUcaggacUUgcagaaUUaaUggaaUg
    676 CUGUCCUAAGGUUGUUGAGUUgUgca
    1046 AAAAGGCAUUGUGGUUUUUG hsa-mir-2455 hsa-mir- 1340 caUUaggUUggUgcAAAAGGCAUUGUGGUUUUUGccUa
    548an UaaaagUaaUggcaaaaaccgcaaUUccUUUUgcaccaaccUaa
    U
    1047 CGGGCGGCGGCUGUGUUGCGCA hsa-mir-2456 pending 1341 cacUcgcgcUgcggccagcgcccgggccUgcgggccCGGGCGGCG
    GCUGUGUUGCGCAgUc
    1048 UAUGGAAGGGAGAAGAGCUUUA hsa-mir-2457 hsa-mir- 1342 UUaUUaaUAUGGAAGGGAGAAGAGCUUUAaUgaUUgga
    3202-1 gUcaUUUUcagagcaUUaaagcUcUUcUcccUUccaUaUUaa
    UgU
    1049 CGGCGGGGACGGCGAUUGGU hsa-mir-1908 hsa-mir- 1343 UgccgCGGCGGGGACGGCGAUUGGUccgUaUgUgUggUg
    1908 ccaccggccgccggcUccgccccggcc
    1050 CCUCCUGCCCUCCUUGCUGUAG hsa-mir-1976 pending 1344 gcaaagggUggcagcaaggaaggcaggggUccUaaggUgUgUCC
    UCCUGCCCUCCUUGCUGUAGacUUUgg
    1051 UGAGCCGAGCUGAGCUUAGCUG hsa-mir-2457 hsa-mir- 1345 UGAGCCGAGCUGAGCUUAGCUGggcUgagcUa
    4537 accagggcUgggcUgagcUgggcUgagcUgagcUgagc
    GAGCUUGGAUGAGCUGGGCUGAacUgggcUgg
    1052 GAGCUUGGAUGAGCUGGGCUGA hsa-mir-2458 hsa-mir- 1346 gUUgagcUgggcUgggcUgagUUgagccaggcUgaU
    4538 cUgggcUgag
    1053 GCUGAACUGGGCUGAGCUGGGC hsa-mir-2459 hsa-mir- 1347 UgagcUgggcUcUgcUgUgcUgUgcUgagcagggcU
    4539 gaGCUGAACUGGGCUGAGCUGGGC
    1054 CUGGGCUGAAUGACAGUGAUGAG hsa-mir-2460 pending 1348 gUcaagUcagaacagccaggUagagcccUUgUccaaac
    CUGGGCUGAAUGACAGUGAUGAG
    1055 GGGAGCCGGGGCUGUGAGAGGA hsa-mir-2461 pending 1349 cUcUUUgagccUUggcUgccUUggUgcagcagggUc
    aUcUgUagggccaccccacagcUcUUUccUUccccUc
    cUcUcUccaGGGAGCCGGGGCUGUGAGAGGA
    1056 UUAGUCCUGCCUGUAGGUUUA hsa-mir-2462 hsa-mir- 1350 aagcUgcaUggaccaggacUUggcaccUUUggccUU
    4540 AGUCCUGCCUGUAGGUUUA
  • TABLE 33
    Primers for Reverse Transcription for a subset of the known miRNAs 
    identified by deep sequencing analysis.
    SEQ Putative Primer for reverse SEQ
    ID Major/Minor Mature Sequence transcription ID
    NO. miRNA ID Captured of miRNA NO.
      7 hsa-mir-129- AAGCCCUUACCCCAAAAAGCAU AAGCCCTTACCCCAAAAAGCAT 1351
    2*
     22 hsa-mir-25* AGGCGGAGACUUGGGCAAUUG AGGCGGAGACTTGGGCAATTG 1352
     24 hsa-mir-30b* CUGGGAGGUGGAUGUUUACUUC CTGGGAGGTGGATGTTTACTTC 1353
     26 hsa-mir-30c- CUGGGAGAAGGCUGUUUACUCU CTGGGAGAAGGCTGTTTACTCT 1354
    2*
     27 hsa-mir-30e* CUUUCAGUCGGAUGUUUACAGC CTTTCAGTCGGATGTTTACAGC 1355
     29 hsa-mir-342- UCUCACACAGAAAUCGCACCCGU TCTCACACAGAAATCGCACCCGT 1356
    3p
     56 hsa-let-7a-2 UGAGGUAGUAGGUUGUAUAGUU TGAGGTAGTAGGTTGTATAGTT 1357
     57 hsa-let-7a-3 UGAGGUAGUAGGUUGUAUAGUU TGAGGTAGTAGGTTGTATAGTT 1358
     58 hsa-let-7c UGAGGUAGUAGGUUGUAUGGUU TGAGGTAGTAGGTTGTATGGTT 1359
     63 hsa-mir-100 AACCCGUAGAUCCGAACUUGUG AACCCGTAGATCCGAACTTGTG 1360
     64 hsa-mir-101-1 UACAGUACUGUGAUAACUGAA TACAGTACTGTGATAACTGAA 1361
     65 hsa-mir-101-2 GUACAGUACUGUGAUAACUGAA TACAGTACTGTGATAACTGAA 1362
     66 hsa-mir-103-1 AGCAGCAUUGUACAGGGCUAUGA AGCAGCATTGTACAGGGCTATGA 1363
     67 hsa-mir-103-2 AGCAGCAUUGUACAGGGCUAUGA AGCAGCATTGTACAGGGCTATGA 1364
     70 hsa-mir-106a AAAAGUGCUUACAGUGCAGGUAG AAAAGTGCTTACAGTGCAGGTAG 1365
     71 hsa-mir-106b UAAAGUGCUGACAGUGCAGAU TAAAGTGCTGACAGTGCAGAT 1366
     72 hsa-mir-107 AGCAGCAUUGUACAGGGCUAUCA AGCAGCATTGTACAGGGCTATCA 1367
     73 hsa-mir-10a UACCCUGUAGAUCCGAAUUUGUG TACCCTGTAGATCCGAATTTGTG 1368
     74 hsa-mir-10b UACCCUGUAGAACCGAAUUUGUG TACCCTGTAGAACCGAATTTGTG 1369
     98 hsa-mir-128-1 UCACAGUGAACCGGUCUCUUU TCACAGTGAACCGGTCTCTTT 1370
     99 hsa-mir-128-2 UCACAGUGAACCGGUCUCUUU TCACAGTGAACCGGTCTCTTT 1371
    100 hsa-mir-129-1 CUUUUUGCGGUCUGGGCUUGC CTTTTTGCGGTCTGGGCTTGC 1372
    101 hsa-mir-129-2 CUUUUUGCGGUCUGGGCUUGC CTTTTTGCGGTCTGGGCTTGC 1373
    103 hsa-mir-1295 UUAGGCCGCAGAUCUGGGUGA TTAGGCCGCAGATCTGGGTGA 1374
    119 hsa-mir-140- UACCACAGGGUAGAACCACGG TACCACAGGGTAGAACCACGG 1375
    3p
    122 hsa-mir-143 UGAGAUGAAGCACUGUAGCUC TGAGATGAAGCACTGTAGCTC 1376
    125 hsa-mir-146a UGAGAACUGAAUUCCAUGGGUU TGAGAACTGAATTCCATGGGTT 1377
    126 hsa-mir-146b UGAGAACUGAAUUCCAUAGGCU TGAGAACTGAATTCCATAGGCT 1378
    127 hsa-mir-148a UCAGUGCACUACAGAACUUUGU TCAGTGCACTACAGAACTTTGT 1379
    130 hsa-mir-151- CUAGACUGAAGCUCCUUGAGG CTAGACTGAAGCTCCTTGAGG 1380
    3p
    131 hsa-mir-152 UCAGUGCAUGACAGAACUUGG TCAGTGCATGACAGAACTTGG 1381
    132 hsa-mir-155 UUAAUGCUAAUCGUGAUAGGGGU TTAATGCTAATCGTGATAGGGGT 1382
    133 hsa-mir-15a UAGCAGCACAUAAUGGUUUGUG TAGCAGCACATAATGGTTTGTG 1383
    134 hsa-mir-15b UAGCAGCACAUCAUGGUUUACA TAGCAGCACATCATGGTTTACA 1384
    135 hsa-mir-16-1 UAGCAGCACGUAAAUAUUGGCG TAGCAGCACGTAAATATTGGCG 1385
    136 hsa-mir-16-2 UAGCAGCACGUAAAUAUUGGCG TAGCAGCACGTAAATATTGGCG 1386
    137 hsa-mir-17 CAAAGUGCUUACAGUGCAGGUAG CAAAGTGCTTACAGTGCAGGTAG 1387
    138 hsa-mir-181a- AACAUUCAACGCUGUCGGUGAGU AACATTCAACGCTGTCGGTGAGT 1388
    1
    139 hsa-mir-181a- AACAUUCAACGCUGUCGGUGAGU AACATTCAACGCTGTCGGTGAGT 1389
    2
    140 hsa-mir-181b- AACAUUCAUUGCUGUCGGUGGGU AACATTCATTGCTGTCGGTGGG 1390
    1
    141 hsa-mir-181b- AACAUUCAUUGCUGUCGGUGGGU AACATTCATTGCTGTCGGTGGG 1391
    2
    142 hsa-mir-181c AACAUUCAACCUGUCGGUGAGU AACATTCAACCTGTCGGTGAGT 1392
    143 hsa-mir-181d AACAUUCAUUGUUGUCGGUGGGU AACATTCATTGTTGTCGGTGGGTT 1393
    147 hsa-mir-185 UGGAGAGAAAGGCAGUUCCUGA TGGAGAGAAAGGCAGTTCCTGA 1394
    150 hsa-mir-18a UAAGGUGCAUCUAGUGCAGAUAG TAAGGTGCATCTAGTGCAGATAG 1395
    151 hsa-mir-191 CAACGGAAUCCCAAAAGCAGCUG CAACGGAATCCCAAAAGCAGCTG 1396
    152 hsa-mir-192 CUGACCUAUGAAUUGACAGCC CTGACCTATGAATTGACAGCC 1397
    153 hsa-mir-193a- UGGGUCUUUGCGGGCGAGAUGA TGGGTCTTTGCGGGCGAGATGA 1398
    5p
    159 hsa-mir-196b UAGGUAGUUUCCUGUUGUUGGG TAGGTAGTTTCCTGTTGTTGGG 1399
    160 hsa-mir-197 UUCACCACCUUCUCCACCCAGC TTCACCACCTTCTCCACCCAGC 1400
    163 hsa-mir-199b ACAGUAGUCUGCACAUUGGUUA ACAGTAGTCTGCACATTGGTTA 1401
    164 hsa-mir-19a UGUGCAAAUCUAUGCAAAACUGA TGTGCAAATCTATGCAAAACTGA 1402
    175 hsa-mir-20a UAAAGUGCUUAUAGUGCAGGUAG TAAAGTGCTTATAGTGCAGGTAG 1403
    176 hsa-mir-20b CAAAGUGCUCAUAGUGCAGGUAG CAAAGTGCTCATAGTGCAGGTAG 1404
    186 hsa-mir-221 AGCUACAUUGUCUGCUGGGUUUC AGCTACATTGTCTGCTGGGTTTC 1405
    187 hsa-mir-222 AGCUACAUCUGGCUACUGGGU AGCTACATCTGGCTACTGGGT 1406
    190 hsa-mir-23a AUCACAUUGCCAGGGAUUUCC ATCACATTGCCAGGGATTTCC 1407
    194 hsa-mir-25 CAUUGCACUUGUCUCGGUCUGA CATTGCACTTGTCTCGGTCTGA 1408
    195 hsa-mir-26a-1 UUCAAGUAAUCCAGGAUAGGCU TTCAAGTAATCCAGGATAGGCT 1409
    196 hsa-mir-26a-2 UUCAAGUAAUCCAGGAUAGGCU TTCAAGTAATCCAGGATAGGCT 1410
    197 hsa-mir-26b UUCAAGUAAUUCAGGAUAGGU TTCAAGTAATTCAGGATAGGT 1411
    198 hsa-mir-27a UUCACAGUGGCUAAGUUCCGC TTCACAGTGGCTAAGTTCCGC 1412
    203 hsa-mir-29a UAGCACCAUCUGAAAUCGGUUA TAGCACCATCTGAAATCGGTTA 1413
    208 hsa-mir-30a UGUAAACAUCCUCGACUGGAAG TGTAAACATCCTCGACTGGAAG 1414
    209 hsa-mir-30b UGUAAACAUCCUACACUCAGCU TGTAAACATCCTACACTCAGCT 1415
    210 hsa-mir-30c-1 UGUAAACAUCCUACACUCUCAGC TGTAAACATCCTACACTCTCAGC 1416
    211 hsa-mir-30c-2 UGUAAACAUCCUACACUCUCAGC TGTAAACATCCTACACTCTCAGC 1417
    212 hsa-mir-30d UGUAAACAUCCCCGACUGGAAG TGTAAACATCCCCGACTGGAAG 1418
    213 hsa-mir-30e UGUAAACAUCCUUGACUGGAAG TGTAAACATCCTTGACTGGAAG 1419
    216 hsa-mir-320a AAAAGCUGGGUUGAGAGGGCGA AAAAGCTGGGTTGAGAGGGCGA 1420
    217 hsa-mir-320b- AAAAGCUGGGUUGAGAGGGCAA AAAAGCTGGGTTGAGAGGGCAA 1421
    1
    218 hsa-mir-320b- AAAAGCUGGGUUGAGAGGGCAA AAAAGCTGGGTTGAGAGGGCAA 1422
    2
    227 hsa-mir-331 GCCCCUGGGCCUAUCCUAGAA GCCCCTGGGCCTATCCTAGAA 1423
    231 hsa-mir-33a GUGCAUUGUAGUUGCAUUGCA GTGCATTGTAGTTGCATTGCA 1424
    233 hsa-mir-340 UUAUAAAGCAAUGAGACUGAUU TTATAAAGCAATGAGACTGATT 1425
    236 hsa-mir-34a UGGCAGUGUCUUAGCUGGUUGU TGGCAGTGTCTTAGCTGGTTGT 1426
    239 hsa-mir-361- UUAUCAGAAUCUCCAGGGGUAC TTATCAGAATCTCCAGGGGTAC 1427
    5p
    241 hsa-mir-363 AAUUGCACGGUAUCCAUCUGUA AATTGCACGGTATCCATCTGTA 1428
    242 hsa-mir-365-2 UAAUGCCCCUAAAAAUCCUUAU TAATGCCCCTAAAAATCCTTAT 1429
    246 hsa-mir-374a UUAUAAUACAACCUGAUAAGUG TTATAATACAACCTGATAAGTG 1430
    250 hsa-mir-378 ACUGGACUUGGAGUCAGAAGG ACTGGACTTGGAGTCAGAAGG 1431
    259 hsa-mir-423 UGAGGGGCAGAGAGCGAGACUUU TGAGGGGCAGAGAGCGAGACTTT 1432
    265 hsa-mir-449a UGGCAGUGUAUUGUUAGCUGGU TGGCAGTGTATTGTTAGCTGGT 1433
    287 hsa-mir-503 UAGCAGCGGGAACAGUUCUGCAG TAGCAGCGGGAACAGTTCTGCAG 1434
    296 hsa-mir-532 CAUGCCUUGAGUGUAGGACCGU CATGCCTTGAGTGTAGGACCGT 1435
    316 hsa-mir-576- AAGAUGUGGAAAAAUUGGAAUC AAGATGTGGAAAAATTGGAATC 1436
    3p
    327 hsa-mir-625 AGGGGGAAAGUUCUAUAGUCC AGGGGGAAAGTTCTATAGTCC 1437
    338 hsa-mir-7-1 UGGAAGACUAGUGAUUUUGUUGU TGGAAGACTAGTGATTTTGTTGT 1438
    339 hsa-mir-7-2 UGGAAGACUAGUGAUUUUGUUGU TGGAAGACTAGTGATTTTGTTGT 1439
    340 hsa-mir-7-3 UGGAAGACUAGUGAUUUUGUUGU TGGAAGACTAGTGATTTTGTTGT 1440
    345 hsa-mir-874 CUGCCCUGGCCCGAGGGACCGA CTGCCCTGGCCCGAGGGACCGA 1441
    351 hsa-mir-9-1 UCUUUGGUUAUCUAGCUGUAUGA TCTTTGGTTATCTAGCTGTATGA 1442
    352 hsa-mir-9-2 UCUUUGGUUAUCUAGCUGUAUGA TCTTTGGTTATCTAGCTGTATGA 1443
    353 hsa-mir-92a-1 UAUUGCACUUGUCCCGGCCUGU TATTGCACTTGTCCCGGCCTGT 1444
    354 hsa-mir-92a-2 UAUUGCACUUGUCCCGGCCUGU TATTGCACTTGTCCCGGCCTGT 1445
    356 hsa-mir-93 CAAAGUGCUGUUCGUGCAGGUAG CAAAGTGCTGTTCGTGCAGGTAG 1446
    357 hsa-mir-9-3 UCUUUGGUUAUCUAGCUGUAUGA TCTTTGGTTATCTAGCTGTATGA 1447
    364 hsa-mir-99a AACCCGUAGAUCCGAUCUUGUG AACCCGTAGATCCGATCTTGTG 1448
    387 hsa-mir-570 AAAGGUAAUUGCAGUUUUUCCC AAAGGTAATTGCAGTTTTTCCCA 1449
  • TABLE 34
    Primers for Reverse Transcription of a subset of novel miRNAs
    identified by deep sequencing analysis.
    SEQ Temporary Primer for Reverse SEQ
    ID Assigned Mature Sequence Transcription ID
    NO. miRNA ID Captured of miRNA NO.
     773 hsa-miR- ACUGGACUUGGAGUCAGGA ACTGGACTTGGAGTCAGGA 1450
    378c
     774 hsa-mir-449c AGGCAGUGUAUUGCUAGCGGCU AGGCAGTGTATTGCTAGCGGCTGT 1451
     775 hsa-mir-500- UGCACCCAGGCAAGGAUUCUGC TGCACCCAGGCAAGGATTCTGC 1452
    2
     784 hsa-mir-2224 UGAGGGAGGAGACUGCA TGAGGGAGGAGACTGCA 1453
     785 hsa-mir-2225 ACUGGACUUGGAGCCAGAAG ACTGGACTTGGAGCCAGAAG 1454
     786 hsa-mir-2226 GUCACUGAUGUCUGUAGCUGAG GTCACTGATGTCTGTAGCTGAGACGG 1455
     787 hsa-mir-2227 GAUGAGGAUGGAUAGCAAGGAA GATGAGGATGGATAGCAAGGAAG 1456
     789 hsa-mir-2229 AAAAGCAUCAGGAAGUACCCA AAAAGCATCAGGAAGTACCCA 1457
     796 hsa-mir-2235 GUCAAAUGAAGGGCUGAUCACG GTCAAATGAAGGGCTGATCACGAAATA 1458
     798 hsa-mir-2237 AGAGUUAACUCAAAAUGGACUA AGAGTTAACTCAAAATGGACTA 1459
     799 hsa-mir-2238 UGUUGGGAUUCAGCAGGACCAU TGTTGGGATTCAGCAGGACCATT 1460
     800 hsa-mir-2239 UAAAUAGAGUAGGCAAAGGACA TAAATAGAGTAGGCAAAGGACA 1461
     805 hsa-mir-2244 AAGAGGAAGAAAUGGCUGGUUC AAGAGGAAGAAATGGCTGGTTCTCAG 1462
     809 hsa-mir-2248 UAGUGGAUGAUGCACUCUGUGC TAGTGGATGATGCACTCTGTGC 1463
     814 hsa-mir-2253 AAAGACUCUGCAAGAUGCCU AAAGACTCTGCAAGATGCCT 1464
     816 hsa-mir-2255 AGGAGAAGUAAAGUAGAA AGGAGAAGTAAAGTAGAA 1465
     817 hsa-mir-2256 AUGGCCAGAGCUCACACAGAGG ATGGCCAGAGCTCACACAGAGG 1466
     819 hsa-mir-2258 AUCAGGGCUUGUGGAAUGGGAA ATCAGGGCTTGTGGAATGGGAAG 1467
     820 hsa-mir-2259 AUGGCCAGAGCUCACACAGAGG ATGGCCAGAGCTCACACAGAGG 1468
     821 hsa-mir-2260 UGAGGAUAUGGCAGGGAAGGGG TGAGGATATGGCAGGGAAGGGGA 1469
     825 hsa-mir-2264 UGGGCUCAGGGUACAAAGGUU TGGGCTCAGGGTACAAAGGTTC 1470
     828 hsa-mir- GCUGCACCGGAGACUGGGUAA GCTGCACCGGAGACTGGGTAA 1471
    2266-1
     829 hsa-mir- GCUGCACCGGAGACUGGGUAA GCTGCACCGGAGACTGGGTAA 1472
    2266-2
     836 hsa-mir-2272 UGUCGUGGGGCUUGCUGGCUUG TGTCGTGGGGCTTGCTGGCTTG 1473
     838 hsa-mir-2274 ACUGGACUUGGAGGCAGAA ACTGGACTTGGAGGCAGAA 1474
     841 hsa-mir-2277 UUGGAGGCGUGGGUUUU TTGGAGGCGTGGGTTTT 1475
     844 hsa-mir-2280 CUGACUGAAUAGGUAGGGUCAU CTGACTGAATAGGTAGGGTCAT 1476
     846 hsa-mir-2282 AGAUUGUUUCUUUUGCCGUGCA AGATTGTTTCTTTTGCCGTGCA 1477
     847 hsa-mir- CACGGCAAAAGAAACAAUCCA CACGGCAAAAGAAACAATCCA 1478
    2282*
     848 hsa-mir-2283 CAGGGCUGGCAGUGACAUGGGU CAGGGCTGGCAGTGACATGGGT 1479
     849 hsa-mir-2284 GGUGGGGGCUGUUGUUU GGTGGGGGCTGTTGTTT 1480
     850 hsa-mir-2285 UGGGGAGGUGUGGAGUCAGCAU TGGGGAGGTGTGGAGTCAGCATG 1481
     852 hsa-mir-2287 GGCUCCUUGGUCUAGGGGUA GGCTCCTTGGTCTAGGGGTA 1482
     856 hsa-mir-2290 UGGGGAUUUGGAGAAGUGGUGA TGGGGATTTGGAGAAGTGGTGA 1483
     857 hsa-mir-2291 AAAAGUGAUUGCAGUGUUUG AAAAGTGATTGCAGTGTTTGCC 1484
     860 hsa-mir-2294 UAGGAGCUCAACAGAUGCCUGU TAGGAGCTCAACAGATGCCTGT 1485
     861 hsa-mir-2295 AGCUUUUGGGAAUUCAGGUAG AGCTTTTGGGAATTCAGGTAG 1486
     864 hsa-mir-2298 CAAAAGUGAUCGUGGUUUUUG CAAAAGTGATCGTGGTTTTTG 1487
     865 hsa-mir-2299 AGGGUGUGUGUGUUUUU AGGGTGTGTGTGTTTTT 1488
     871 hsa-mir-2305 ACUGACAGGAGAGCAUUUUGA ACTGACAGGAGAGCATTTTGA 1489
     874 hsa-mir-2308 AUAGUGGUUGUGAAUUUACCUU ATAGTGGTTGTGAATTTACCTTC 1490
     876 hsa-mir-2310 CUACCCCAGGAUGCCAGCAUAG CTACCCCAGGATGCCAGCATAGTT 1491
     877 hsa-mir-2311 ACUGGACUUGGUGUCAGAUGG ACTGGACTTGGTGTCAGATGG 1492
     880 hsa-mir-2314 UAGUGGAUGAUGGAGACUCGGU TAGTGGATGATGGAGACTCGGT 1493
     888 hsa-mir-2322 AAGGUUUGGAUAGAUGCAAUA AAGGTTTGGATAGATGCAATA 1494
     889 hsa-mir-2323 AAAGGUAAUUGCAGUUUUUCCC AAAGGTAATTGCAGTTTTTCCCA 1495
     890 hsa-mir-2324 AGGGGACCAAAGAGAUAUAUAG AGGGGACCAAAGAGATATATAG 1496
     896 hsa-mir-2328 GGCGACAAAACGAGACCCUGU GGCGACAAAACGAGACCCTGTC 1497
     897 hsa-mir-2329 GGGUGCGGGCCGGCGGGG GGGTGCGGGCCGGCGGGGT 1498
     899 hsa-mir-2331 CAUGCUAGGAUAGAAAGAAUGG CATGCTAGGATAGAAAGAATGG 1499
     901 hsa-mir-2333 GCAAAGUGAUGAGUAAUACUGG GCAAAGTGATGAGTAATACTGG 1500
     915 hsa-mir-2346 CCCUGGGGUUCUGAGGACAUG CCCTGGGGTTCTGAGGACATG 1501
     917 hsa-mir-2348 CAGGAAGGAUUUAGGGACAGGC CAGGAAGGATTTAGGGACAGGC 1502
     919 hsa-mir-2350 AUUAAGGACAUUUGUGAUUGAU ATTAAGGACATTTGTGATTGAT 1503
     920 hsa-mir- AAAAGGCAUAAAACCAAGACA AAAAGGCATAAAACCAAGACA 1504
    2351-1
     921 hsa-mir- AAAAGGCAUAAAACCAAGACA AAAAGGCATAAAACCAAGACA 1505
    2351-2
     924 hsa-mir- UAAAAACUGCAAUUACUUUC TAAAAACTGCAATTACTTTC 1506
    2354-1
     926 hsa-mir- UGUGAUAUCAUGGUUCCUGGGA TGTGATATCATGGTTCCTGGGA 1507
    2355-1
     929 hsa-mir- UGUGAUAUCAUGGUUCCUGGGA TGTGATATCATGGTTCCTGGGA 1508
    2355-2
     931 hsa-mir- UGUGAUAUCAUGGUUCCUGGGA TGTGATATCATGGTTCCTGGGA 1509
    2355-3
     932 hsa-mir- UGUGAUAUCGUGCUUCCUGGGA TGTGATATCGTGCTTCCTGGGA 1510
    2355b
     936 hsa-mir-2358 AAAAGUAACUGCGGUUUUUGA AAAAGTAACTGCGGTTTTTGA 1511
     938 hsa-mir-2360 GGAGUGGGCUGGUGGUU GGAGTGGGCTGGTGGTT 1512
     940 hsa-mir- AAGGGCUUCCUCUCUGCAGGAC AAGGGCTTCCTCTCTGCAGGAC 1513
    2362-1
     941 hsa-mir- AAGGGCUUCCUCUCUGCAGGAC AAGGGCTTCCTCTCTGCAGGAC 1514
    2362-2
     949 hsa-mir-2370 AGAGCUGGCUGAAGGGCAG AGAGCTGGCTGAAGGGCAG 1515
     953 hsa-mir-2374 UGUGACUUUAAGGGAAAUGGCG TGTGACTTTAAGGGAAATGGCG 1516
     954 hsa-mir-2375 UCUCAGGAGUAAAGACAGAGUU TCTCAGGAGTAAAGACAGAGTT 1517
     955 hsa-mir-2376 AGGUGGAUGCAAUGUGACCUCA AGGTGGATGCAATGTGACCTCA 1518
     977 hsa-mir-2397 AGGCUGGGCUGGGACGGA AGGCTGGGCTGGGACGGA 1519
     979 hsa-mir-2399 UAGGAUGGGGGUGAGAGGUG TAGGATGGGGGTGAGAGGTG 1520
     988 hsa-mir-2406 UGAGGGAGUAGGAUGUAUGGUU TGAGGGAGTAGGATGTATGGTT 1521
     991 hsa-mir-2409 AGACUGACGGCUGGAGGCCCAU AGACTGACGGCTGGAGGCCCAT 1522
     994 hsa-mir-2412 UAGUGAGUUAGAGAUGCAGAGC TAGTGAGTTAGAGATGCAGAGC 1523
     996 hsa-mir-2414 GGGAGAAGGGUCGGGGC GGGAGAAGGGTCGGGGC 1524
    1002 hsa-mir-2416 CUCGUGGGCUCUGGCCACGGC CTCGTGGGCTCTGGCCACGGCC 1525
    1003 hsa-mir- AGAAGGGGUGAAAUUUAAACGU AGAAGGGGTGAAATTTAAACGT 1526
    2417-1
    1004 hsa-mir- AGAAGGGGUGAAAUUUAAACGU AGAAGGGGTGAAATTTAAACGT 1527
    2417-2
    1005 hsa-mir- AGAAGGGGUGAAAUUUAAACGU AGAAGGGGTGAAATTTAAACGT 1528
    2417-3
    1007 hsa-mir-2419 GCUCAGGGAUGAUAACUGUGCUGAGA GCTCAGGGATGATAACTGTGCTGAGA 1529
    1011 hsa-mir-2423 CUGGACUGAGCCAUGCUACUGG CTGGACTGAGCCATGCTACTGG 1530
    1017 hsa-mir-2428 AUAGCAGCAUGAACCUGUCUCA ATAGCAGCATGAACCTGTCTCA 1531
    1018 hsa-mir- UGAGACAGGCUUAUGCUGCUAU TGAGACAGGCTTATGCTGCTAT 1532
    2428*
    1022 hsa-mir-2432 UGGUCUGCAAAGAGAUGACUGU TGGTCTGCAAAGAGATGACTGTG 1533
    1025 hsa-mir-2435 UUGGAGGGUGUGGAAGACAUC TTGGAGGGTGTGGAAGACATC 1534
    1027 hsa-mir-2437 AUGGAGAAGGCUUCUGA ATGGAGAAGGCTTCTGA 1535
    1028 hsa-mir-2438 AAAAGCUGGGUUGAGAA AAAAGCTGGGTTGAGAAG 1536
    1029 hsa-mir-2439 UGGAAGGUAGACGGCCAGAGAG TGGAAGGTAGACGGCCAGAGAG 1537
    1030 hsa-mir-2440 UCUGGGAGGUUGUAGCAGUGGA TCTGGGAGGTTGTAGCAGTGGA 1538
    1036 hsa-mir-2445 GGAGGAACCUUGGAGCUUCGGC GGAGGAACCTTGGAGCTTCGGCA 1539
    1038 hsa-mir-2447 ACUGGACUAGGAGUCAGAAGG ACTGGACTAGGAGTCAGAAGG 1540
    1041 hsa-mir-2450 CAAAAACUGCAGUUACUUUUGU CAAAAACTGCAGTTACTTTTGT 1541
    1046 hsa-mir-2455 AAAAGGCAUUGUGGUUUUUG AAAAGGCATTGTGGTTTTTG 1542
  • TABLE 35
    miRNAs that differentiate ABC DLBCL vs.
    GCB DLBCL
    FoldChange pVal
    ABC vs. ABC vs.
    MicroRNA GCB GCB
    UGGUCUGCAAAGAGAUGACUGUG −4.30138 0.001335
    (SEQ ID NO. 1565)
    CAAAAACUGCAGUUACUUUUGU −3.52085 0.022949
    (SEQ ID NO. 1041)
    UGGGGAUUUGGAGAAGUGGUGA −2.8374 0.000753
    (SEQ ID NO. 856)
    hsa-miR-129-3p −2.48708 7.39E−05
    ACUGGACUUGGUGUCAGAUGG −1.3712 0.01173
    (SEQ ID NO. 877)
    hsa-miR-196b −1.28463 0.032606
    hsa-miR-9 −1.00737 0.003176
    hsa-miR-28-5p −0.82319 0.00026
    hsa-miR-365 −0.78573 0.032749
    hsa-miR-185 −0.75345 0.044082
    hsa-miR-199b-3p −0.74898 0.015518
    hsa-miR-152 −0.67388 0.001282
    hsa-miR-23a −0.65979 0.028732
    hsa-miR-193a-5p −0.54233 0.031154
    hsa-miR-27a −0.49729 0.027207
    hsa-miR-331-3p −0.47573 0.0128
    hsa-miR-301a −0.45261 0.014231
    hsa-miR-128 −0.4224 0.024065
    AGAUUGUUUCUUUUGCCGUGCA 0.557435 0.02141
    (SEQ ID NO. 846)
    hsa-miR-625 0.747299 0.01813
    hsa-miR-155 0.781901 0.024175
    hsa-miR-20b 0.986918 0.000746
    GGCUCCUUGGUCUAGGGGUA 1.945372 0.002596
    (SEQ ID NO. 852)
    UAGUGAGUUAGAGAUGCAGAGC 2.347695 0.009081
    (SEQ ID NO. 994)
    CAGGAAGGAUUUAGGGACAGGC 2.519326 0.04483
    (SEQ ID NO.-917)
    *The 3′-end G of SEQ ID NO. 1565 is optionally omitted (providing SEQ ID NO. 1022).
  • APPENDIX A
    Average expression of the genes depicted in FIG. 6*
    Naïve
    vs Germinal Germinal
    Germinal Center vs Center vs
    Center Plasma Memory
    Naïve GC GC PC GC
    Aver- Aver- aver- Aver- Aver- Memory
    ID Gene Name age age age age age Average
    1 VPS37B 10.60 4.58 4.58 9.71
    2 SCN3A 9.50 3.98
    3 NT5E 10.76 5.69
    4 TBC1D9 12.03 7.03 7.03 11.19 7.03 12.88
    5 MAP7 1.64 8.03
    6 SPRY1 10.40 5.72
    7 TNFSF12 8.11 3.54 3.54 7.55
    8 SOCS3 9.00 4.48 4.48 9.39
    9 EDG1 11.43 6.91 6.91 8.69
    10 CTGF 7.62 3.30 3.30 9.65
    11 FAM46A 10.65 6.46 6.46 8.29
    12 MOBKL2B 11.63 7.45
    13 DNMT3A 10.56 6.44 6.44 7.85
    14 BHLHB2 10.75 6.64 6.64 10.96
    15 LAMC1 9.85 5.80 5.80 9.67
    16 CD69 13.27 9.40 9.40 12.27
    17 PLEKHA1 10.95 7.20
    18 PTGDR 7.20 3.46
    19 TXNIP 14.89 11.20 11.20 13.39 11.20 15.10
    20 SIDT1 11.52 7.86 7.86 9.38
    21 LY6E 8.57 4.92 4.92 7.39
    22 IGF1R 8.73 5.13
    23 PRICKLE1 11.68 8.09 8.09 9.69
    24 CSDA 12.12 8.59 8.59 10.10
    25 KLF2 12.61 9.10 9.10 11.70
    26 ELOVL2 7.32 3.86
    27 CCND2 12.06 8.61 8.61 11.53
    28 LASS6 10.29 6.86 6.86 9.42 6.86 9.48
    29 DUSP6 11.93 8.53 8.53 10.19
    30 CUGBP2 14.28 10.93 10.93 14.29
    31 PTPRO 9.64 6.32 6.32 8.63
    32 PHF16 10.33 7.04
    33 NR3C2 8.85 5.58
    34 CRTC3 12.56 9.32 9.32 11.11
    35 ADAMTS6 7.68 4.45
    36 ETV6 10.36 7.14 7.14 8.89 7.14 10.43
    37 LRRC17 3.10 7.49
    38 FAM46C 12.18 8.98 8.98 14.76 8.98 10.54
    39 SATB2 7.20 4.02 4.02 7.60
    40 RNF125 9.00 5.83
    41 ST6GALNAC3 8.12 4.96
    42 LARGE 9.05 5.89 5.89 8.73
    43 ZNF276 9.39 6.25
    44 KCNA3 4.83 9.82
    45 BCL2 10.89 7.76 7.76 11.41
    46 MTSS1 12.92 9.82 9.82 12.05
    47 NR6A1 9.10 6.03 6.03 7.62
    48 BHLHB3 11.11 8.05 8.05 13.26 8.05 13.26
    49 MYO10 7.22 4.19
    50 ITM2C 6.44 13.85
    51 C18orf1 9.49 6.47 6.47 8.63
    52 FXYD7 7.36 4.35
    53 DUSP8 7.96 4.96 4.96 8.41 4.96 7.75
    54 BTBD3 7.41 4.42
    55 TMEPAI 11.15 8.20 8.20 11.03
    56 ANTXR2 9.90 6.97
    57 FOSB 10.13 7.21 7.21 11.05
    58 TMCC3 8.23 5.31 5.31 7.09 5.31 8.05
    59 ARL4C 11.31 8.41 8.41 10.32
    60 ZMYND11 11.33 8.43 8.43 11.34 8.43 11.68
    61 RHOBTB1 7.33 4.48
    62 JUN 12.14 9.34 9.34 12.70
    63 SKI 10.46 7.67 7.67 10.68
    64 TMEM121 7.07 4.29
    65 IL13RA1 8.99 6.21
    66 KIF13B 6.23 9.01
    67 BHLHB5 4.26 7.39
    68 PGM2L1 10.35 7.65
    69 C14orf4 12.11 9.47 9.47 11.01 9.47 11.65
    70 PDE4B 12.38 9.74 9.74 11.60
    71 PDE7B 8.64 6.03
    72 BCL9L 9.37 6.77 6.77 8.61
    73 PCDH9 10.32 7.73
    74 ARHGAP5 10.44 7.86 7.86 9.11 7.86 9.85
    75 KIAA0802 9.18 6.61 6.61 7.91 6.61 7.89
    76 ITGB4 7.48 4.91
    77 NOTCH2NL 7.17 8.95
    78 CDC42BPA 7.32 4.77
    79 SPG20 9.25 6.73
    80 KLF4 10.04 7.57 7.57 9.09
    81 AHNAK 9.34 6.87 6.87 9.56 6.87 11.51
    82 FCHSD1 9.15 6.69
    83 KIAA1622 3.94 7.67
    84 PLXNC1 10.92 8.48
    85 TMEM150 8.39 5.96
    86 ACVR2A 7.81 5.38 5.38 8.63 5.38 7.40
    87 KALRN 5.61 7.64
    88 ANK2 7.69 5.28 5.28 7.54 5.28 7.00
    89 FLJ14213 7.61 5.21 5.21 7.97
    90 CHPT1 10.92 8.52
    91 TCF2 5.69 7.82
    92 FGF5 5.41 7.52
    93 SLC12A6 12.18 9.80 9.80 11.09
    94 MGC17330 11.53 9.16
    95 NR4A2 10.21 7.85 7.85 9.21 7.85 10.54
    96 SLC39A10 11.06 8.70
    97 LITAF 12.52 10.18 10.18 11.82
    98 AKT3 9.32 6.99 6.99 9.25
    99 PDCD4 12.89 10.57 10.57 13.33
    100 STMN3 10.03 7.72
    101 SIDT2 13.13 10.85
    102 GRIA3 7.04 4.77
    103 EML4 12.83 10.57
    104 DIP2B 11.26 8.99 8.99 10.77
    105 FBN1 4.89 8.17
    106 FAM84B 9.21 6.96
    107 EGR3 11.59 9.35 9.35 8.24 9.35 10.62
    108 CTHRC1 4.25 11.94
    109 RRAGD 7.69 5.46
    110 MACF1 12.88 10.66
    111 FOXF2 7.05 4.83
    112 GAB1 8.01 5.81 5.81 10.91
    113 ST18 4.42 7.40
    114 ZFP36L2 13.78 11.59 11.59 13.43 11.59 14.05
    115 GAB2 8.29 6.12 6.12 9.02
    116 CHST11 11.17 8.99 8.99 10.28
    117 CLOCK 9.85 7.68 7.68 9.91 7.68 9.62
    118 PREX1 10.07 7.90 7.90 11.16
    119 KLF11 8.08 5.94 5.94 8.39
    120 PTGER4 11.66 9.53
    121 KLF9 9.47 7.34 7.34 9.27
    122 FLJ37078 7.55 5.42 5.42 7.49
    123 ODZ2 7.20 5.08 5.08 7.25 5.08 7.22
    124 SESN3 11.24 9.11 9.11 7.60
    125 PDK4 7.22 5.09
    126 CNTNAP3 7.35 5.23 5.23 7.10
    127 DUSP1 13.34 11.22
    128 MARCKS 11.19 9.07 9.07 11.05 9.07 12.21
    129 SPRY4 7.02 4.91
    130 LMO1 4.75 7.16
    131 MTUS1 7.77 5.66 5.66 8.16
    132 ADCY9 8.01 5.91 5.91 7.74
    133 SLC17A6 3.80 7.06
    134 NOX4 7.45 5.37 5.37 7.22
    135 UTRN 9.46 10.97
    136 ZBTB10 8.50 6.45
    137 SLC26A7 8.37 6.32 6.32 7.89
    138 PNRC1 13.14 11.09
    139 LLGL2 6.83 9.29
    140 CHST1 7.15 5.12
    141 CREB3L2 10.53 8.51 8.51 13.30
    142 DDIT4 12.69 10.68
    143 C20orf108 8.82 6.80 6.80 10.19
    144 CDH1 3.85 10.26
    145 TFAP4 7.28 5.29
    146 SLC38A2 13.57 11.58 11.58 13.74 11.58 13.17
    147 SESN1 9.84 7.87 7.87 9.13
    148 YPEL2 10.18 8.20 8.20 10.04
    149 GRASP 8.47 6.50
    150 TSC22D3 13.22 11.26 11.26 12.67
    151 ATP11A 9.70 7.75 7.75 9.50
    152 L3MBTL3 10.61 8.66 8.66 10.06
    153 SORT1 7.61 5.67 5.67 8.11
    154 CAV1 4.80 9.11
    155 RXRA 9.07 7.15 7.15 8.81
    156 CRELD1 8.40 6.48 6.48 8.26
    157 RBMS1 12.40 10.49 10.49 8.80
    158 LYST 10.90 8.99
    159 PIP5K1B 9.61 7.70 7.70 9.97
    160 JUNB 11.62 9.72
    161 MBOAT1 4.80 7.27
    162 IRF4 11.16 9.28 9.28 13.66
    163 LIFR 4.62 7.08
    164 MORC3 11.25 9.37
    165 MBP 11.91 10.05 10.05 8.61
    166 SRC 4.98 7.98
    167 ALS2CR13 11.79 9.93 9.93 8.89 9.93 11.47
    168 MYH1 4.40 7.37
    169 DUSP3 9.36 7.50 7.50 9.16
    170 HLX1 7.14 5.28 5.28 7.65
    171 CDKN1A 9.09 7.23 7.23 8.97 7.23 8.43
    172 SOCS5 10.00 8.15
    173 PPP1R9A 5.14 7.35
    174 TGFBR2 12.81 10.99 10.99 12.63
    175 LRRC16 8.47 6.66
    176 ZNF629 8.17 6.35 6.35 8.58
    177 RPS6KA5 11.75 9.95 9.95 11.48
    178 SATB1 12.79 10.99 10.99 9.06
    179 SEMA4C 7.38 5.59 5.59 8.49 5.59 7.14
    180 ULK1 7.79 5.99 5.99 8.72 5.99 8.06
    181 STX3 8.88 7.09 7.09 8.91
    182 BAMBI 4.81 7.26
    183 MAP3K5 10.63 8.84 8.84 7.66 8.84 10.71
    184 KIAA1147 11.70 9.91 9.91 11.53
    185 SBK1 5.20 7.04
    186 RYR3 7.80 6.02 6.02 8.27
    187 ZNF238 13.05 11.27 11.27 10.08 11.27 12.54
    188 IL12A 5.65 7.26
    189 SLC2A3 12.00 10.23 10.23 11.89
    190 GFPT2 3.39 7.18
    191 G0S2 7.72 5.96
    192 LYRM5 10.29 8.53 8.53 10.93
    193 SSH2 11.67 9.91 9.91 11.85
    194 NRP1 7.44 5.69 5.69 7.22
    195 LMLN 8.92 7.19
    196 UCP3 7.71 5.99
    197 TMEM166 7.31 5.60
    198 CACNA1I 7.46 5.76 5.76 7.06
    199 PHOSPHO1 3.55 7.10
    200 CRIM1 9.79 8.11 8.11 9.32
    201 GATA6 5.41 7.59
    202 SACS 10.06 8.39 8.39 10.54
    203 CDKN1B 12.91 11.24 11.24 14.41
    204 CACNA2D2 5.25 7.57 5.25 7.93
    205 MKRN3 3.65 7.10
    206 MTFR1 10.40 8.74 8.74 7.34 8.74 10.15
    207 GALNT3 10.19 8.54
    208 RPS6KA3 12.07 10.42 10.42 11.48
    209 DTNA 5.47 7.86
    210 MAGI2 7.04 5.40 5.40 7.42
    211 FOXJ2 10.01 8.38 8.38 9.97 8.38 9.85
    212 KIAA0513 5.29 8.44 5.29 7.36
    213 NDRG1 7.75 10.02
    214 AKAP7 10.16 8.54
    215 CD72 13.74 12.12
    216 IGFBP5 7.30 5.69 5.69 7.59
    217 REPS2 7.51 5.92 5.92 7.60
    218 PRDM12 7.17 5.57
    219 ZNF3 8.86 7.27 7.27 8.75
    220 TLL2 4.88 7.01
    221 PCNX 9.77 8.19
    222 ARHGAP24 11.31 9.73 9.73 8.65 9.73 11.32
    223 THRAP2 11.31 9.73
    224 RNF11 9.72 8.15 8.15 11.08
    225 HOXC8 7.05 5.48
    226 SCML2 10.33 8.76
    227 BMPR2 9.70 8.14 8.14 10.06
    228 STAC 5.27 7.20
    229 C10orf54 9.12 7.56 7.56 10.16
    230 FBXL17 9.51 7.95 7.95 9.36
    231 CBX7 10.87 9.32 9.32 10.96
    232 UBE2W 9.80 8.25 8.25 9.76 8.25 9.38
    233 ProSAPiP1 4.12 7.54
    234 UBL3 10.73 9.18 9.18 11.27 9.18 11.03
    235 TTYH3 7.35 5.81 5.81 8.16
    236 PUNC 5.39 8.85 5.39 7.30
    237 GDF11 7.01 5.47 5.47 7.70
    238 LMX1A 5.25 7.43
    239 TIMP2 7.51 5.97 5.97 7.69 5.97 7.40
    240 NHLH2 3.93 7.35
    241 CLCF1 10.50 8.98
    242 ITGB3 7.66 6.14
    243 TMEM132E 3.93 7.20
    244 KCTD17 7.45 5.94 5.94 7.33
    245 ChGn 7.75 6.24 6.24 8.36
    246 DIP2C 9.25 7.75
    247 DKFZp667G2110 8.79 7.28 7.28 9.25
    248 CSNK1G3 10.84 9.34 9.34 10.70
    249 NRIP1 11.79 10.30
    250 SMAD3 10.72 9.23 9.23 7.74 9.23 10.54
    251 SHOX2 7.05 5.57
    252 LDLRAP1 6.80 9.84 6.80 8.59
    253 SUPT3H 7.77 6.30 6.30 8.05
    254 KCNN2 7.18 5.70
    255 DLL1 7.37 5.90
    256 CEND1 7.72 6.26
    257 NOTCH1 10.90 9.45
    258 TLE1 7.74 9.63
    259 FCHO2 8.75 7.30
    260 JPH4 7.12 5.67 5.67 7.60
    261 KCNMB2 7.16 5.72
    262 KHDRBS2 7.17 5.73
    263 LEFTY1 4.38 7.21
    264 ST3GAL5 10.59 9.15
    265 LGR4 5.30 7.29
    266 FNDC8 4.25 8.01
    267 NPTXR 5.87 7.65
    268 PRICKLE2 5.47 7.47
    269 GRIA4 5.19 7.04
    270 RHOB 8.66 7.23 7.23 9.56
    271 ZADH2 8.65 7.22
    272 ZBTB41 9.73 8.31 8.31 9.42
    273 GPRASP2 6.00 7.35
    274 SYS1 10.79 9.36
    275 RUNX1T1 7.37 5.95
    276 DLX2 4.66 7.04
    277 SLC30A7 11.58 10.17
    278 PER1 8.82 7.40
    279 NT5C3 12.67 11.25
    280 PDE3A 11.62 10.21
    281 OCRL 8.07 6.66 6.66 8.04
    282 PSD3 7.99 6.60
    283 LPHN1 7.80 6.41
    284 TNRC6B 11.87 10.48 10.48 11.77
    285 SNN 12.03 10.64 10.64 8.91 10.64 12.10
    286 HERPUD2 11.56 10.18
    287 UBQLNL 7.45 6.07
    288 HES7 7.37 5.99
    289 GALNT2 10.08 8.69 8.69 10.63
    290 CAMKK1 8.45 7.07
    291 ELN 5.44 7.18
    292 ICK 8.09 6.72 6.72 8.01
    293 POU4F2 7.09 5.72 5.72 7.21
    294 GAS2 7.13 5.76 5.76 7.81
    295 ARHGEF3 10.11 8.75 8.75 11.04
    296 ZBTB4 11.45 10.09 10.09 11.78
    297 CHD7 12.14 10.78 10.78 12.08
    298 TMEM45B 5.97 7.61
    299 CLDN11 5.74 7.22
    300 PTPN1 10.85 9.51
    301 PHF20 12.00 10.67
    302 VAV3 10.44 7.84
    303 CARKL 8.38 7.06 7.06 8.94
    304 TRIM36 5.43 7.77
    305 CTLA4 6.57 7.95
    306 POLK 9.69 8.38 8.38 10.55
    307 WSB1 13.22 11.91 11.91 13.02
    308 ALS2CR2 9.87 8.57 8.57 10.14
    309 PLK2 4.94 7.13
    310 SRPK2 10.83 9.53 9.53 11.13
    311 ARRDC2 10.86 9.55
    312 IER5 13.10 11.80
    313 EPN1 8.95 7.66 7.66 9.07
    314 SLC20A2 9.45 8.16
    315 DLG4 4.23 7.22
    316 TMTC2 6.16 7.92
    317 ETV1 8.19 6.90
    318 JAZF1 11.93 10.65 10.65 7.49
    319 VAV2 10.22 8.94
    320 C15orf27 7.19 5.91
    321 FYCO1 9.75 8.47
    322 KIAA0789 7.27 6.00
    323 OBFC2A 9.94 8.66 8.66 10.94
    324 MCF2 7.19 5.92
    325 KIAA2018 11.77 10.50 10.50 9.50
    326 MTMR10 10.75 9.48
    327 FAM63B 6.03 7.83 6.03 7.95
    328 SNF1LK 10.20 8.93 8.93 10.18
    329 ZNF385 8.89 7.63
    330 SESTD1 11.05 9.78
    331 SLC31A2 5.41 9.13
    332 PCMTD1 12.03 10.76 10.76 12.44
    333 NBEA 8.06 6.81 6.81 8.02 6.81 8.35
    334 ZNF295 9.24 10.61
    335 SIPA1L3 10.81 9.57
    336 CC2D1B 9.11 7.87
    337 PRKAG2 7.12 8.42
    338 PKD1 9.04 7.81
    339 CNTNAP2 7.54 6.32
    340 FNBP1L 7.90 6.67
    341 HEXIM1 10.27 9.05 9.05 10.24
    342 C19orf2 12.29 11.07
    343 MYLIP 11.62 10.41 10.41 11.81
    344 SLC11A2 9.27 8.06
    345 CLU 9.92 8.71
    346 GCN5L2 10.18 8.97
    347 DKFZP564J0863 10.85 9.65 9.65 11.11
    348 CNNM2 7.85 6.64 6.64 8.07
    349 CDC42SE1 12.07 10.87 10.87 12.18
    350 HOXB9 6.20 8.41
    351 NFATC3 11.39 10.19
    352 UNC84B 11.12 9.93 9.93 8.59
    353 DUSP5 6.23 9.44
    354 ING1 11.35 10.17
    355 ITM2B 11.23 13.62
    356 FAM53B 11.67 10.49
    357 ZFP36L1 14.07 12.89 12.89 10.09
    358 NIPA1 9.75 8.57 8.57 10.07
    359 GALNT1 10.93 9.76 9.76 11.12
    360 MYPN 4.25 7.32
    361 ITPK1 10.03 8.86
    362 TTYH2 7.90 6.73
    363 DOCK10 10.80 9.63 9.63 11.53
    364 C14orf28 9.18 8.01 8.01 9.58 8.01 9.50
    365 RP11-130N24.1 4.76 7.62
    366 FGF12 5.82 7.33
    367 ATP2B2 7.93 6.76
    368 PPP1R9B 9.77 8.60
    369 PPP3CA 13.50 12.33 12.33 13.86
    370 TFAP2A 5.54 8.26
    371 CYLD 10.91 9.75
    372 PHF1 11.85 10.69 10.69 12.26
    373 NEBL 7.98 6.82 6.82 8.08
    374 ACIN1 12.04 10.89 10.89 11.99
    375 SPTBN1 12.28 11.14 11.14 12.53 11.14 12.42
    376 VAMP4 10.81 9.67 9.67 11.18
    377 DNAJB9 10.80 9.66 9.66 15.21 9.66 11.03
    378 ZDHHC2 11.55 10.42
    379 TRIO 10.57 9.43
    380 TMEM25 6.24 8.57
    381 TAF9B 10.82 9.69
    382 ARID3A 8.03 6.90 6.90 9.81
    383 KIAA0182 10.68 9.55
    384 RPS6KA2 8.61 7.49
    385 C3orf58 11.47 10.34
    386 CAST 11.94 10.82
    387 SH3PXD2A 8.46 7.34
    388 RAB6B 5.93 7.36
    389 RNF141 11.47 10.35
    390 SP4 11.26 10.14
    391 ARMCX2 9.44 8.32 8.32 9.54
    392 ZNF398 10.39 9.28
    393 PBX3 9.69 8.58 8.58 7.00
    394 FOS 12.35 11.25 11.25 13.34
    395 FHOD3 6.40 7.94
    396 C20orf59 10.11 9.01 9.01 10.92
    397 FAM117A 11.67 10.57 10.57 12.06 10.57 11.64
    398 ATP8B2 8.58 7.49 7.49 10.87 7.49 8.88
    399 UXS1 9.53 8.43
    400 GOLGA8A 12.84 11.74 11.74 13.14 11.74 13.05
    401 SUFU 6.03 7.84
    402 NAGPA 9.32 8.23
    403 MLLT6 11.70 10.61
    404 CPEB4 9.46 8.36 8.36 12.21
    405 TMEM50B 10.67 9.58 9.58 11.41 9.58 10.63
    406 AMPD3 11.65 10.56 10.56 8.76
    407 SIX5 5.19 7.53
    408 MMP16 5.66 7.47
    409 LBH 11.87 10.79 10.79 8.83
    410 POM121 9.60 11.26
    411 ATP8B1 11.93 10.86 10.86 8.88
    412 ARHGAP29 3.75 7.60
    413 ZNF395 11.78 10.76
    414 CRY2 6.50 8.01
    415 BIN1 10.68 9.67
    416 PSAP 11.24 13.41 11.24 12.71
    417 ISL1 5.91 7.60
    418 DNAJB5 8.04 6.97
    419 KIAA0284 6.42 8.79
    420 RBM35B 11.44 10.38
    421 ADCY7 11.53 10.47
    422 ARRDC3 9.46 10.68
    423 MICAL1 11.72 10.67
    424 MTHFR 10.31 9.26
    425 HOOK3 8.57 7.53 7.53 6.52
    426 EFNB3 5.16 7.79
    427 ARHGAP12 9.86 8.82
    428 LMBR1L 9.33 8.29
    429 FGF7 5.88 7.86
    430 USP2 5.50 7.52
    431 SMARCA2 11.14 10.12
    432 ELL2 8.23 13.60
    433 C1orf26 7.06 10.01
    434 CXCR4 14.61 13.45
    435 HDGFRP3 5.58 7.39
    436 BNC2 6.18 7.72
    437 YPEL3 10.16 11.81 10.16 11.47
    438 PPFIA3 4.58 8.06
    439 DLGAP4 9.34 10.68
    440 ZBTB7A 9.84 11.10
    441 D4S234E 5.90 7.38
    442 FNDC3A 9.41 13.60
    443 FOXC1 5.84 7.39
    444 KIF26B 5.55 7.30
    445 NAV2 6.26 7.90
    446 DDX3Y 8.07 10.38
    447 FGD1 7.31 6.06
    448 HTR4 7.26 9.01 7.26 8.40
    449 C22orf31 5.67 8.10
    450 RNF44 11.48 10.14
    451 GALNAC4S-6ST 10.43 12.71
    452 CCNT2 10.15 11.23
    453 CHIC1 8.91 10.02
    454 NNAT 5.97 8.19 5.97 7.84
    455 CTDP1 6.81 8.26
    456 BTG1 14.95 13.94
    457 CMTM4 5.27 7.81
    458 GOLGA8B 11.37 12.63
    459 HBP1 10.07 12.13
    460 GDPD1 6.35 7.61
    461 CDYL 9.31 10.61 9.31 10.50
    462 ZNF217 10.77 9.73
    463 KIF5A 6.13 7.75
    464 C1QL1 5.80 8.11
    465 SOLH 7.88 9.03
    466 ZC3H6 9.81 10.96
    467 LATS2 7.61 10.19
    468 COL18A1 6.46 7.85
    469 C11orf24 9.89 11.07
    470 SCUBE3 6.14 7.88
    471 SEMA4G 5.57 7.81
    472 FOXP1 12.31 10.84
    473 TRIB2 10.62 9.61
    474 LOC285382 5.35 7.20
    475 RUNX2 7.91 10.22
    476 LOC196463 4.16 7.52
    477 LPGAT1 10.57 7.99
    478 RASSF2 12.52 10.93
    479 IRF1 9.86 11.60
    480 RAB40B 7.31 10.89
    481 CTDSPL 6.37 7.83
    482 CLCN4 7.44 6.39
    483 CACNB1 6.41 8.20
    484 SYNGR1 8.45 10.40
    485 ST8SLA4 10.67 11.81
    486 PLD3 7.63 10.59
    487 FOXO3A 10.17 12.41
    488 TSPAN33 10.49 9.38
    489 HIST1H4F 6.20 8.08
    490 LAPTM4A 12.05 13.06
    491 PRKCB1 12.14 10.50
    492 PROX1 6.38 7.89
    493 CDK5R1 10.12 7.78
    494 MAP3K9 7.96 9.13
    495 GPX3 5.92 7.61
    496 GNS 8.79 11.06
    497 ARL15 8.27 6.51
    498 OXR1 9.21 11.17 9.21 10.25
    499 AAK1 7.38 9.54 7.38 8.47
    500 SH3PX3 6.72 8.58
    501 MS4A7 10.55 8.35
    502 FLJ20273 5.96 11.23 5.96 8.65
    503 ISCU 12.01 13.55
    504 ITGA2 5.70 7.60
    505 ME1 5.87 7.89
    506 LRP1 4.92 7.04
    507 ZNF652 9.66 10.81
    508 TRAK1 11.07 9.85
    509 SLC8A1 6.27 7.83
    510 C1orf119 10.76 11.98
    511 KLF6 11.33 9.24 11.33 12.40
    512 TRIM2 6.22 8.20
    513 USP3 11.11 12.51
    514 ARID5B 11.02 12.48
    515 RASD1 6.15 9.32
    516 ZCCHC2 10.63 8.93
    517 LEFTY2 5.08 7.03
    518 BACH1 9.97 11.76
    519 IRAK1 11.48 12.80
    520 RP11-217H1.1 10.76 13.04
    521 HLCS 6.54 8.45
    522 NAGK 10.94 12.14
    523 CELSR2 6.26 7.89
    524 PCBP4 7.75 9.08
    525 FLJ25476 9.49 10.72
    526 TPP1 12.10 11.06
    527 ACVR1 7.95 9.31
    528 EHD3 8.99 10.35
    529 FAM80B 9.35 8.02
    530 SPRYD3 8.19 9.51
    531 PRDM4 9.81 10.83
    532 C6orf134 7.92 5.60
    533 HSP90B1 12.04 16.36
    534 DYNC1I1 5.98 7.33
    535 NFLX 7.43 8.67
    536 DOCK4 5.96 7.97
    537 ZNF287 7.09 8.47
    538 XRN1 10.92 12.37
    539 YES1 6.39 8.60
    540 RBM35A 8.19 9.44
    541 HOXB4 7.58 9.27
    542 OTUD7B 7.24 8.57
    543 CELSR3 6.83 8.39
    544 RHOC 7.71 8.84
    545 ZNF607 8.10 6.95
    546 XYLT1 10.28 8.78 10.28 8.86
    547 FAM89B 9.16 10.75
    548 OSBPL8 12.99 11.66
    549 SRCRB4D 6.82 8.67
    550 RASL12 5.05 8.07
    551 NAG8 8.39 9.78
    552 MAN1A2 10.83 12.15
    553 PPARA 8.59 9.65
    554 CLDN12 6.66 8.39
    555 ID4 5.93 7.79
    556 HECTD2 7.98 6.80
    557 EFCAB4A 5.93 8.96
    558 CREBL1 6.97 8.09
    559 SARM1 6.98 8.29
    560 MIDN 8.48 7.29
    561 EMB 10.48 8.65
    562 FOXK2 8.40 9.63
    563 INADL 6.87 8.44
    564 KCNAB1 6.26 9.76
    565 MAP3K8 10.92 9.60
    566 C8orf58 7.89 5.62
    567 SLC4A7 9.82 8.52 9.82 10.90
    568 RAB8B 12.46 10.92
    569 C10orf118 8.93 10.20
    570 CRTC2 9.37 7.94
    571 KLC2 7.31 9.19
    572 SRCAP 8.06 6.96
    573 CNTFR 7.15 8.67
    574 SPTBN2 4.75 7.11
    575 SMAD7 8.69 9.93
    576 NDFIP1 9.10 10.95
    577 BCL11A 14.03 10.63
    578 SFXN5 7.26 8.87
    579 RIMBP2 5.93 8.33
    580 FUT8 8.62 11.08
    581 PSEN2 5.86 9.17
    582 MAP6 5.22 7.37
    583 FOXO1A 11.53 10.14
    584 BTG2 11.81 13.82
    585 C10orf56 6.93 9.30
    586 MAPK1 12.06 10.36
    587 ZBTB47 6.63 8.12
    588 GOSR2 9.73 11.07
    589 ZFP90 10.15 8.92
    590 RALGPS1 8.02 9.38
    591 DGKI 4.77 7.39
    592 RGL2 11.08 9.55
    593 PAK6 5.90 8.55
    594 DMXL1 11.85 10.31
    595 TMEM113 12.28 11.03
    596 SNX24 6.75 8.53
    597 HOXA3 5.99 8.27
    598 SAMD4A 9.84 8.36
    599 WDR45 9.88 12.43
    600 TLOC1 12.91 14.52
    601 LARP2 7.64 11.50
    602 DTX2 7.60 6.20
    603 ITGA9 7.53 6.32
    604 FASTK 10.04 11.22
    605 TAOK2 7.47 6.37
    606 CRTAP 9.78 11.08
    607 SERTAD2 11.91 10.82
    608 TBP 10.14 9.09
    609 IQGAP2 7.26 11.19 7.26 8.93
    610 RASGEF1B 6.23 8.01
    611 PIP5K2B 9.69 8.53
    612 PRRC1 10.32 11.92
    613 RHPN2 6.73 8.21
    614 DYRK1B 5.92 7.61
    615 ADCY2 5.98 7.97
    616 C12orf34 5.61 7.09
    617 GMPR 5.35 8.15
    618 PAK2 10.86 9.66
    619 KIAA1539 8.12 9.49
    620 PLAGL1 10.03 6.68
    621 LCORL 9.74 11.29
    622 BCL9 7.21 9.16
    623 CPEB2 9.09 10.23
    624 TMEM59 12.10 14.75
    625 TRIP10 7.17 9.36
    626 CCPG1 8.38 11.86
    627 NDE1 10.71 9.30
    628 ZDHHC21 9.38 8.11
    629 STOX2 5.87 7.66
    630 RAB4B 10.63 8.66
    631 LRRFIP1 13.25 11.99
    632 OSBP 10.10 11.39
    633 RAB6A 10.76 12.27
    634 RHOV 4.88 7.19
    635 SLC39A14 8.80 11.00
    636 ADARB1 10.05 7.69
    637 ESPN 6.85 8.19
    638 SEC31A 11.64 13.61
    639 PJA2 10.85 11.99
    640 SYNGR3 9.01 7.56
    641 LOC339745 11.94 10.54
    642 NEDD9 11.23 12.48
    643 COL23A1 5.41 7.02
    644 PIP5K3 11.93 10.79
    645 PTPRG 7.30 8.49
    646 DAB2IP 5.61 8.30
    647 MAPRE3 5.80 8.60
    648 SQSTM1 10.05 11.45
    649 RAB6C 10.88 12.04
    650 FAM57A 7.58 6.18
    651 YPEL5 12.41 13.78
    652 TTN 9.61 7.03
    653 HTRA3 5.62 8.02
    654 CHST2 7.80 12.49
    655 BAZ1A 11.43 10.06
    656 LRFN5 7.38 6.21
    657 MBNL1 14.10 12.62
    658 MLL2 10.93 9.89
    659 SF1 11.44 10.36
    660 FRMPD1 4.80 7.06
    661 PPP2R5B 7.60 9.12
    662 RNF43 10.04 8.01
    663 GAP43 5.07 7.49
    664 NOMO1 11.11 14.31
    665 VEGFA 7.79 9.36
    666 C22orf5 8.75 11.38
    667 AKAP11 11.79 10.64
    668 INSIG2 9.46 11.32
    669 PDIK1L 9.11 10.72
    670 TMEM4 10.93 13.32
    671 LMNA 7.80 9.75
    672 TP53INP1 11.84 14.14
    673 NAV1 6.96 8.31
    674 SPTY2D1 9.25 10.77
    675 CREBL2 9.95 11.10
    676 MFAP3L 5.90 7.46
    677 REXO2 10.96 13.71
    678 SPTBN4 6.77 8.22
    679 NOMO2 9.74 12.94
    680 PTEN 12.78 11.40
    681 FBXL16 6.86 9.56
    682 GPM6A 7.87 6.15 7.87 6.67
    683 PRX 6.76 8.91
    684 HOXC11 6.40 7.88
    685 KIAA0329 8.27 9.87
    686 PAFAH1B1 11.68 10.33
    687 C20orf174 9.58 7.27
    688 MTPN 13.87 12.17
    689 TMED5 12.25 14.41
    690 FURIN 8.03 9.54
    691 ELAVL3 4.66 8.01
    692 SH2B3 10.31 8.87
    693 LIN28B 5.99 7.58
    694 KIAA1033 12.65 11.38
    695 TMEM28 4.95 7.14
    696 TBC1D15 10.30 11.52
    697 GOLGA4 10.11 11.71
    698 STX1A 5.63 7.82
    699 SLC40A1 6.87 8.27
    700 KIAA1815 9.18 7.93
    701 HNT 5.53 7.09
    702 PDE11A 5.72 7.82
    703 TGFBR3 7.84 9.52
    704 MTF1 9.92 8.86
    705 MAN1A1 9.99 13.65
    706 THRA 7.26 8.48
    707 CBLB 11.46 9.08
    708 SLC35F1 6.29 8.16
    709 FOXP4 8.52 7.30
    710 ELOVL5 13.83 12.78
    711 NMUR1 4.13 7.31
    712 ITPR1 12.06 9.69
    713 CDCA7L 11.95 10.33
    714 RASSF1 9.35 10.69
    715 IL1RAPL1 6.42 8.18
    716 AUH 9.37 11.19
    717 DIAPH1 11.52 9.74
    718 ENSA 12.33 11.22
    719 FAM43A 10.62 9.39
    720 CSMD3 4.79 7.58
    721 SLC25A37 10.10 8.69
    722 SLC33A1 9.78 12.19
    723 CNOT6 9.98 8.93
    724 GRID1 7.05 8.80
    725 C21orf91 11.51 10.18
    726 ITPKB 11.28 8.91
    727 CP 5.89 7.41
    728 HMBOX1 10.05 8.50
    729 ARID1A 12.22 11.11
    730 C5orf5 11.86 10.38
    731 TMSB4X 16.86 15.10
    732 EPAS1 7.02 8.39
    733 HPS3 11.65 10.16
    734 DKK1 6.16 7.86
    735 ZNF282 7.89 5.40
    736 AP3D1 11.29 12.84
    737 DERL1 11.69 13.43
    738 C5orf13 9.89 7.62
    739 CCNG2 13.32 11.64
    740 PGRMC2 9.44 11.38
    741 ARF6 13.60 12.55
    742 TMEM110 7.75 9.24
    743 FAM13A1 7.11 9.69
    744 BRMS1L 8.58 10.18
    745 TRAM1 12.52 15.17
    746 CALU 9.42 11.20
    747 GOLPH3 11.55 12.81
    748 MAP3K7 11.14 10.06
    749 ABCG4 6.90 8.22
    750 NELF 8.75 7.70
    751 ADIPOR1 9.67 10.92
    752 INSR 8.48 11.62
    753 GRM5 6.24 7.65
    754 TFG 10.76 12.30
    755 USP48 11.91 13.09
    756 CLCN6 9.26 7.48
    757 ZNF219 6.11 8.42
    758 C7orf43 8.34 6.62
    759 NFKB1 11.90 10.70
    760 ARF3 11.11 9.87
    761 JMJD1C 12.34 11.11
    762 ROD1 13.13 11.42
    763 OXSR1 10.69 9.15
    764 ERGIC2 10.86 12.81
    765 EIF4E3 7.61 9.87
    766 SEC24A 10.05 12.85
    767 SPRED1 7.19 5.77
    768 HNRPH3 12.60 11.38
    769 ZDHHC7 10.34 9.05
    770 HNRPA1 16.14 15.14
    771 TMED2 12.01 14.26
    772 VASP 10.60 8.60
    773 CHD4 11.40 10.31
    774 RTN4RL1 5.48 8.36
    775 PPP1R12A 12.03 10.97
    776 SGK3 9.58 11.68
    777 ARHGAP17 12.37 8.62
    778 GORASP2 11.28 13.30
    779 C2orf44 8.38 6.72
    780 FAM116A 11.12 10.08
    781 SSR1 12.75 14.73
    782 MYH9 11.24 9.89
    783 PIK3CD 12.99 10.03
    784 DAZAP2 14.26 13.23
    785 SEL1L 10.74 14.04
    786 LOC388284 7.05 8.32
    787 THRB 7.51 6.11 7.51 6.29
    788 MGAT2 11.91 14.44
    789 C8orf13 9.35 6.47
    790 PDZD2 7.00 4.39
    791 DERL2 10.74 12.75
    792 ZCCHC5 7.39 6.27
    793 NFYC 10.27 9.03
    794 GLUD2 8.88 7.58
    795 ESR1 7.55 9.88
    796 NRP2 6.51 8.13
    797 NUS1 10.01 11.53
    798 BIRC6 12.15 10.94
    799 ARID3B 7.83 9.22
    800 STCH 10.16 13.88
    801 SLC7A11 6.32 8.00
    802 OSBPL5 7.91 9.22 7.91 6.62
    803 IGFBP3 5.60 7.61
    804 LNPEP 13.72 11.05
    805 ZNRF1 8.18 9.68
    806 DDAH1 7.96 5.87
    807 ERG 4.07 7.49
    808 APLP2 10.90 8.38
    809 ZNFX1 10.14 8.93
    810 GPM6B 8.66 6.69
    811 BLCAP 11.49 10.10
    812 SRP68 11.47 12.88
    813 PIK3AP1 14.12 11.74
    814 ANKRD28 11.00 12.46
    815 KCNH8 8.27 4.80
    816 KIAA0430 12.43 10.61
    817 PPP2R1B 9.84 8.41
    818 TMED9 11.62 13.82
    819 CTNNBIP1 7.31 8.89
    820 PPP2R5D 9.51 7.92
    821 CBX4 12.36 13.69
    822 AKAP6 7.38 5.55 7.38 4.93
    823 C2orf30 10.72 13.84
    824 DR1 11.97 10.65
    825 MTDH 12.46 13.96
    826 ETS1 14.40 12.62
    827 EPHA8 6.12 8.10
    828 ANKRD13B 7.23 5.85
    829 C4orf16 8.83 7.70
    830 SOX4 9.14 10.20
    831 SLC12A2 10.23 9.01
    832 IER3IP1 11.35 12.56
    833 DST 7.02 8.34
    834 WRNIP1 11.03 9.49
    835 CLCC1 9.63 11.48
    836 B4GALT6 7.90 6.82
    837 BTBD10 10.12 8.07
    838 SDC1 7.05 12.14
    839 C10orf12 10.32 8.40
    840 ZDHHC3 9.80 8.78
    841 GNAI2 10.86 9.27
    842 HNRPU 13.82 12.47
    843 GNAZ 8.86 7.26
    844 ALG9 8.93 10.97
    845 FBXL10 11.75 10.43
    846 ARID4B 12.19 10.96
    847 PPP1R3F 6.19 7.79
    848 EPB49 6.49 7.94
    849 PCNP 12.91 11.74
    850 PCYT1B 11.35 9.77
    851 RAB14 11.64 10.41
    852 TCERG1 12.50 11.46
    853 MKNK2 14.87 12.67
    854 COL4A3 8.78 12.23
    855 HNRPA0 12.50 11.36
    856 P2RX4 8.88 10.29
    857 JUP 9.23 5.70
    858 EGR2 10.43 8.07
    859 SUPT16H 11.35 9.60
    860 PNRC2 13.93 11.64
    861 SRPR 11.87 13.89
    862 BPTF 12.46 11.34
    863 RBM16 12.05 10.52
    864 YWHAZ 13.62 12.61
    865 EDEM3 11.01 12.76
    866 C12orf23 11.18 12.40
    867 DOC2A 3.96 7.21
    868 SETD2 11.54 10.39
    869 FAM98A 10.91 12.10
    870 C13orf18 13.25 9.86
    871 BRP44L 10.48 11.91
    872 CCDC6 11.25 9.82
    873 GLCCI1 12.22 15.19
    874 PLEKHH1 7.03 9.25
    875 SMEK1 11.38 10.37
    876 ANKRD9 4.70 8.61
    877 CSNK1E 8.86 11.48
    878 DCUN1D3 7.48 5.95
    879 LTB 14.66 9.91
    880 EOMES 7.30 6.14
    881 PARP8 10.81 8.69
    882 ABCD1 7.12 8.49
    883 HOXA10 5.56 7.32
    884 RNPS1 12.60 11.25
    885 AYTL2 12.08 10.79
    886 FLJ20699 5.74 8.80
    887 SAPS1 11.43 9.76
    888 SYNJ1 8.36 9.64
    889 ZNF403 12.06 10.91
    890 KPNB1 13.37 12.26
    891 ISOC1 9.67 10.98
    892 HYOU1 9.95 11.85
    893 ZNF706 12.83 14.30
    894 HDLBP 10.60 13.37
    895 ELF1 12.70 11.34
    896 TM9SF4 8.66 10.55
    897 RAB8A 11.94 10.88
    898 MORF4L2 12.94 14.69
    899 SERP1 13.31 15.16
    900 ADAMTS5 5.71 7.31
    901 TRIOBP 11.23 10.18
    902 ZNF664 11.32 12.57
    903 RAB11FIP1 11.78 9.03
    904 MYO18A 8.06 6.19
    905 DUSP10 10.13 8.70
    906 ATXN1 6.66 10.65 6.66 10.25
    907 EPB41L4B 6.12 7.95
    908 CNTNAP1 6.51 9.06
    909 SLC17A7 6.47 8.01
    910 SPCS2 13.75 15.53
    911 CCNC 12.68 14.10
    912 WDR77 10.67 8.83
    913 GMFB 12.03 10.70
    914 ITGA6 6.72 10.51
    915 CASP8AP2 10.55 9.44
    916 SEC24D 8.79 11.88
    917 CBX1 12.16 10.96
    918 TBX3 6.05 7.89
    919 NFAT5 12.09 10.72
    920 ATP6V1B2 10.73 9.53
    921 ACTG1 16.72 14.81
    922 RND3 7.31 5.65
    923 HNRPUL1 11.97 10.58
    924 TJP1 7.18 10.59
    925 RAPGEF4 5.25 8.09
    926 RGMA 5.65 7.42
    927 NAP1L1 14.70 12.60
    928 TARDBP 12.72 11.49
    929 DAZAP1 12.74 11.30
    930 ZNF609 8.26 6.94 8.26 9.52
    931 ARL1 10.44 12.41
    932 ERC2 7.03 5.97
    933 PDE4A 7.65 9.22
    934 CSK 12.83 10.59
    935 IMPAD1 8.44 10.05
    936 PNN 13.75 12.48
    937 DCP2 13.06 10.74
    938 PIK3R3 6.34 7.82
    939 RAB1A 13.59 14.83
    940 CENTB2 12.39 10.97
    941 SPTAN1 11.48 9.79
    942 DNAJC8 12.25 11.00
    943 UNC13B 6.70 8.35
    944 DHX15 14.19 12.99
    945 VEZF1 11.45 9.94
    946 DHDDS 8.74 10.05
    947 FAM55C 8.19 9.74
    948 USP37 8.89 7.60
    949 MMD 11.68 10.32
    950 HCLS1 14.42 13.12
    951 KIAA1370 13.30 14.72
    952 GANC 8.31 6.12
    953 SSRP1 11.34 10.27
    954 G3BP1 12.24 10.55
    955 BAAT 4.91 7.24
    956 FNDC3B 8.27 14.34
    957 FBXW7 10.21 12.19
    958 SPECC1L 10.27 7.66
    959 YBX1 15.31 14.20
    960 YAP1 7.23 5.61
    961 ARF4 12.09 14.23
    962 PNKD 10.86 9.79
    963 CLEC2D 11.96 10.90
    964 XPO1 13.81 11.82
    965 TRAM2 9.38 12.80
    966 MITF 8.05 6.41
    967 CFL1 16.37 14.09
    968 CREB5 5.46 7.24
    969 GREM1 4.48 7.14
    970 LONRF1 11.26 10.00
    971 NME7 9.37 8.30
    972 PMAIP1 12.26 10.75
    973 KLHL14 11.89 10.84
    974 AOF1 9.33 7.96 9.33 8.28
    975 SMPD3 5.90 7.83
    976 RGL1 6.66 8.04
    977 LYPD6 5.38 7.39
    978 STAT5B 10.95 9.73
    979 C10orf6 10.04 8.44
    980 CLDND1 10.72 12.01
    981 DUSP9 5.59 7.70
    982 SLC36A1 8.53 7.23
    983 PAM 8.90 10.86
    984 GHR 5.87 7.56
    985 CBL 11.69 10.26
    986 CENTG2 5.96 7.39
    987 BACH2 13.68 9.35 13.68 11.88
    988 NUP153 12.33 10.55
    989 CPD 8.37 9.72
    990 APLN 8.58 6.47
    991 RFXDC2 11.67 10.00
    992 GABRB2 5.58 8.10
    993 NOMO3 5.39 7.39
    994 RHOJ 6.41 7.75
    995 PRDM1 9.15 14.10
    996 IGSF3 7.62 5.91
    997 UBE2A 12.47 11.47
    998 KBTBD8 12.82 9.73 12.82 11.71
    999 PRR15 7.27 5.94 7.27 4.67
    1000 ILF3 11.94 10.71
    1001 WIPF1 13.81 12.41
    1002 GCNT2 11.01 8.49
    1003 DBNL 10.43 8.48
    1004 C14orf43 10.14 8.01
    1005 MID1IP1 9.16 8.11
    1006 LIMD2 10.43 8.88
    1007 HNRPK 14.49 12.95 14.49 13.46
    1008 ZNF697 5.74 8.07
    1009 TSHZ3 7.31 5.32
    1010 MBNL2 11.88 13.47
    1011 ELL 7.83 9.17
    1012 MAFB 7.30 8.56
    1013 GGA2 13.25 10.77
    1014 C20orf121 10.01 8.93
    1015 CDC2L6 11.52 9.69
    1016 TOB2 11.39 9.58
    1017 MAP4K4 12.04 10.41
    1018 FAM102A 11.41 10.18
    1019 ITGB3BP 11.86 10.76
    1020 HIVEP1 10.35 9.05
    1021 NUDT21 12.51 11.11
    1022 EIF4A1 14.02 12.98
    1023 TSPAN14 8.38 6.31
    1024 SLC2A4RG 8.98 7.40
    1025 DGKZ 9.74 7.85
    1026 PTPN9 9.30 7.85
    1027 BCL7A 11.33 10.10
    1028 LSM14A 12.74 11.19
    1029 GNB2 11.50 10.12
    1030 SLC6A6 11.35 8.51
    1031 TACC1 13.21 11.62
    1032 LIMK2 9.80 8.12
    1033 ACVR2B 6.69 8.33
    1034 SCC-112 12.25 10.55
    1035 PTBP1 13.38 12.19 13.38 12.21
    1036 CITED2 9.88 12.56
    1037 SNX5 14.17 13.16
    1038 ACTR2 15.12 13.32
    1039 OSBPL3 10.59 12.84
    1040 SFRS1 14.60 13.24
    1041 ADM 7.24 11.10
    1042 PFKFB3 11.91 10.01
    1043 FNBP1 13.61 12.25
    1044 MTMR2 10.53 9.06
    1045 DDHD1 10.18 8.74
    1046 HSPA5 13.70 16.32
    1047 PTK2 12.12 8.33
    1048 UBE2I 13.17 11.22
    1049 SNAP23 13.78 12.23
    1050 MTERFD2 10.53 8.59
    1051 COTL1 13.89 10.14
    1052 PHACTR2 8.65 6.86
    1053 GLRA2 5.93 7.69
    1054 NUTF2 10.39 9.26
    1055 TSGA14 9.52 8.03
    1056 FKBP1A 12.16 10.89 12.16 10.82
    1057 LRRC1 8.82 7.68
    1058 PDIA6 13.07 14.91
    1059 YWHAQ 14.50 12.99
    1060 ACHE 5.59 8.29
    1061 KRAS 12.36 10.49
    1062 FAM107B 13.87 12.55
    1063 CCDC117 11.03 9.56
    1064 WDR1 13.38 11.36
    1065 HMGB1 16.36 14.98 16.36 14.97
    1066 CCND3 12.69 9.79
    1067 SUV39H1 9.28 8.07
    1068 RANBP5 11.94 10.87
    1069 SLC25A33 10.24 9.00
    1070 EDNRA 5.94 7.12
    1071 RAB11A 12.94 11.73
    1072 DDEF1 11.98 10.54
    1073 CXorf15 11.84 10.47
    1074 C4orf34 13.65 10.16
    1075 SLC44A1 11.10 13.50
    1076 EIF2AK3 12.29 13.83
    1077 RAP1B 14.21 13.21
    1078 CDK2 10.20 8.73 10.20 9.01
    1079 JDP2 7.94 5.97
    1080 GSTCD 8.86 7.85
    1081 TNKS2 10.95 9.62 10.95 9.62
    1082 FUZ 7.15 8.96 7.15 8.19
    1083 SYPL1 13.56 10.87
    1084 EIF4H 13.07 12.02
    1085 PIP5K2A 9.65 8.06
    1086 RGS2 11.61 14.48
    1087 ARF5 10.35 9.13
    1088 JAKMIP2 8.57 6.96
    1089 RABGAP1 12.19 9.65 12.19 10.85
    1090 LRIG1 9.76 10.77 10.77 9.16
    1091 CLTA 13.08 11.71
    1092 APBB2 7.87 6.39
    1093 SMC1A 12.88 11.33
    1094 CDC27 9.86 10.88
    1095 STT3A 8.64 9.66
    1096 ZFAND6 12.01 13.04 13.04 11.95
    1097 BZRAP1 8.43 7.15
    1098 DPP3 9.41 10.44 10.44 8.39
    1099 CNIH 11.94 12.98
    1100 TMEM16F 9.42 10.46
    1101 ARHGEF7 11.99 13.03 13.03 11.18 13.03 11.60
    1102 CAMTA1 10.60 11.64
    1103 PFN1 14.03 15.08
    1104 USP12 10.18 11.23
    1105 AZIN1 11.24 12.29
    1106 GNA13 13.89 14.94 14.94 13.37
    1107 RCOR1 10.46 11.51 11.51 9.96
    1108 USP1 13.36 11.52
    1109 VANGL1 7.47 9.15
    1110 CAPZB 11.85 12.91
    1111 CDV3 13.86 14.91
    1112 ABI1 11.61 12.67 12.67 10.96
    1113 ST5 7.21 8.28
    1114 TTL 8.63 9.69 9.69 8.03
    1115 ANP32E 12.76 13.82 13.82 12.19
    1116 USP7 12.27 13.34
    1117 BCL11B 7.20 8.27 8.27 9.68
    1118 OAZ2 8.98 10.06
    1119 PPP2CA 12.04 13.12 13.12 11.89
    1120 TSC1 10.58 11.66
    1121 CTDSPL2 9.81 10.90 10.90 9.51 10.90 9.68
    1122 NEDD4L 7.81 8.90
    1123 NAT13 12.06 13.16
    1124 ASF1A 9.54 10.64
    1125 DPF1 7.18 8.50 7.18 5.84
    1126 RAN 13.46 14.57 14.57 12.39
    1127 ELAVL1 11.66 12.77 12.77 11.43
    1128 GRHL1 5.76 7.24
    1129 SMAD2 10.45 11.57
    1130 IQWD1 9.70 10.83 10.83 9.73
    1131 ETS2 7.50 5.66
    1132 CDC25B 10.04 11.18
    1133 USP32 10.65 11.78 11.78 10.75
    1134 EED 11.76 12.90 12.90 11.50
    1135 CTNND2 5.93 7.81
    1136 SHROOM3 7.86 9.01 9.01 6.05
    1137 PSCD3 6.43 7.57
    1138 ATF7 7.83 8.97
    1139 CDK6 10.31 11.46
    1140 GCH1 12.59 10.17
    1141 AP3S1 11.95 13.12
    1142 ARL6IP1 12.03 13.20 13.20 11.51
    1143 TBC1D1 11.00 12.17 12.17 10.01
    1144 ATP2A2 10.75 11.92 11.92 10.76
    1145 SORL1 12.49 13.67 13.67 10.58
    1146 SOX5 9.30 10.47 10.47 7.33 10.47 9.08
    1147 KIAA1411 8.65 9.83
    1148 KIAA0922 12.43 13.61 13.61 10.86 13.61 12.35
    1149 SSX2IP 7.82 9.00 9.00 7.49
    1150 SNRPD1 11.85 13.04
    1151 EDD1 11.23 12.42
    1152 BLMH 9.01 10.21
    1153 PTPLB 11.32 12.52
    1154 SLC25A27 7.44 3.28
    1155 PGAM1 12.40 13.61 13.61 12.55
    1156 HMGA1 11.26 12.47 12.47 10.36
    1157 EDEM1 11.34 12.55
    1158 PRPF38A 10.27 11.48 11.48 10.00
    1159 DCUN1D1 9.82 11.03
    1160 ROBO1 7.43 8.64
    1161 LRRC59 11.26 12.65
    1162 ZNF207 12.29 13.51
    1163 GTDC1 9.19 10.42 10.42 9.35
    1164 C1orf121 10.47 11.70
    1165 NF1 9.23 10.46
    1166 CUL3 12.98 14.21 14.21 12.80 14.21 12.99
    1167 B4GALT5 8.74 9.97 9.97 8.08 9.97 8.71
    1168 GADD45A 8.14 9.37 9.37 11.74
    1169 RASD2 5.53 7.35
    1170 CD4 6.76 8.01 8.01 6.11
    1171 WWC1 6.16 7.88
    1172 DUSP2 9.43 10.69 10.69 9.18
    1173 TP53INP2 8.44 9.70 9.70 8.53 9.70 8.00
    1174 NRAS 8.89 10.16
    1175 TFRC 12.12 13.39 13.39 11.88
    1176 MASTL 8.76 10.03 10.03 8.23 10.03 8.64
    1177 USP6 9.12 10.39 10.39 9.25
    1178 VGLL4 10.30 11.57 11.57 10.16
    1179 C10orf78 8.93 10.21
    1180 BTG3 9.87 11.16
    1181 TMOD2 8.64 9.93 9.93 6.94
    1182 HOXA5 7.03 8.32
    1183 AK2 10.33 11.62
    1184 MAP2K1 10.41 11.71 11.71 10.69 11.71 10.61
    1185 CASP3 10.16 11.47
    1186 STK40 9.30 10.60 10.60 8.13
    1187 GRHL3 5.20 7.46
    1188 SLC25A4 8.65 9.96
    1189 KLHDC5 9.52 10.83
    1190 SAMHD1 9.72 11.03
    1191 PHLPP 7.93 9.24 9.24 7.58
    1192 CCNE1 7.86 9.18
    1193 EGR1 11.92 13.24
    1194 PIM1 9.44 10.76 10.76 8.87
    1195 HECW1 6.49 7.81
    1196 CHAC1 6.73 8.76
    1197 P4HA2 6.84 8.18
    1198 PPM1E 6.59 7.92
    1199 KIAA0746 13.65 14.98
    1200 LOC401720 6.33 7.63
    1201 CAPN5 5.90 7.24
    1202 DYNLL1 12.69 14.03
    1203 EHMT1 10.40 11.75
    1204 RIC8B 7.54 8.89
    1205 GRIN1 7.40 8.93
    1206 DEK 12.73 14.09 14.09 10.29
    1207 E2F1 7.01 8.37 8.37 7.21
    1208 FAM45A 10.66 12.02
    1209 VAMP1 11.10 12.47
    1210 LTBP1 7.23 8.61
    1211 SOCS1 9.18 10.56 10.56 9.25
    1212 ZCCHC14 6.98 8.36
    1213 KLHL3 8.04 9.43
    1214 RET 5.90 7.29 7.29 5.99
    1215 CUTL1 10.33 11.72 11.72 10.67 11.72 10.50
    1216 RBL1 7.58 8.98 8.98 7.52 8.98 7.97
    1217 TOP1 11.47 12.87
    1218 GPD1L 7.94 9.35
    1219 SAR1B 9.03 10.46 10.46 12.55
    1220 MTF2 11.84 13.27 13.27 11.18
    1221 ANP32B 15.53 14.21
    1222 CIT 8.19 9.63 9.63 7.43 9.63 7.77
    1223 POU3F1 6.08 7.52
    1224 MTMR12 11.44 12.89 12.89 11.13 12.89 11.60
    1225 MBOAT2 6.73 8.17 8.17 6.25
    1226 DOCK9 9.28 10.73
    1227 ZAK 8.60 10.05 10.05 8.21
    1228 LOC152485 11.05 12.51 12.51 10.56
    1229 HNRPA3 14.33 12.26
    1230 LMNB1 10.63 8.78
    1231 ZFYVE21 8.42 9.90
    1232 TXNDC5 12.47 16.40
    1233 UBE2G1 11.36 12.84
    1234 KIF23 7.44 8.93 8.93 5.57 8.93 6.64
    1235 DPYSL2 9.98 11.46 11.46 9.03
    1236 ATP5G3 12.15 13.64
    1237 GLRX5 10.08 11.57
    1238 NLK 10.41 11.92
    1239 ARL6IP6 10.51 12.02 12.02 10.43
    1240 CNNM4 6.17 7.68 7.68 5.21
    1241 TBC1D4 9.12 10.64 10.64 8.94
    1242 CD163 5.49 7.00
    1243 PKD2 8.17 9.71 9.71 7.48
    1244 DIAPH3 8.23 9.77 9.77 8.34
    1245 RAD23B 10.65 12.20 12.20 10.54
    1246 DCAMKL2 5.53 7.08 7.08 5.88
    1247 LMBR1 7.22 8.77
    1248 RRAS2 11.24 12.79 12.79 11.03
    1249 MYO1D 6.31 7.88 7.88 10.07
    1250 KLHL5 10.57 12.15 12.15 10.43 12.15 10.80
    1251 EPS15 12.32 13.91 13.91 12.70
    1252 FASLG 5.47 7.06
    1253 H2AFY 12.56 14.16
    1254 LIMA1 8.47 10.07 10.07 9.06
    1255 CDCA4 8.92 10.52 10.52 9.16
    1256 HAS3 5.70 7.31 7.31 6.15
    1257 HRBL 5.96 7.57 7.57 6.35 7.57 5.97
    1258 SYAP1 9.71 11.32 11.32 9.76
    1259 MDFIC 12.06 13.67
    1260 FAM76B 11.27 12.89 12.89 10.52
    1261 SNTB2 8.22 9.85 9.85 8.64
    1262 ARL3 8.92 10.55
    1263 GPR124 5.50 7.14
    1264 BCL2L11 10.79 12.43 12.43 11.14
    1265 RNF103 12.03 13.23
    1266 MYB 6.97 8.62 8.62 5.61
    1267 PKM2 11.21 12.87
    1268 VCL 8.92 10.57 10.57 8.25
    1269 RBBP7 12.45 14.11 14.11 12.96 14.11 12.70
    1270 LBR 12.86 14.53 14.53 12.16 14.53 12.50
    1271 RRBP1 6.97 8.64 8.64 11.94
    1272 GABRB3 5.33 7.00
    1273 SGCB 7.78 9.45 9.45 8.22
    1274 FAM81A 6.61 8.30 8.30 5.44
    1275 RAB15 5.75 7.44
    1276 SOX9 6.72 8.42
    1277 SAP30 8.22 9.91
    1278 BRWD1 8.60 10.30 10.30 8.72 10.30 9.04
    1279 KCNMA1 7.47 9.17 9.17 10.42
    1280 WHSC1 9.67 11.37 11.37 9.60
    1281 CCDC126 9.36 11.09
    1282 GRAMD1C 7.83 9.57
    1283 PHF19 8.98 10.73 10.73 9.18
    1284 ADAM23 7.02 8.77 8.77 7.00
    1285 C9orf150 5.38 7.13
    1286 ZNF572 6.52 8.30 8.30 6.82
    1287 STK39 9.38 11.15 11.15 9.40
    1288 SMS 9.73 11.54
    1289 DMD 8.96 10.77 10.77 9.32
    1290 C1orf83 6.15 7.96
    1291 MFHAS1 9.80 11.61 11.61 9.36
    1292 STXBP1 6.57 7.79
    1293 CPNE2 5.44 7.27 7.27 4.84
    1294 MYH10 7.07 8.90 8.90 7.85
    1295 CALM3 9.63 11.46 11.46 10.30
    1296 EFNB2 7.01 8.85
    1297 ACTN1 5.89 7.74
    1298 RBMS3 5.67 7.51
    1299 ACOT7 9.70 7.83
    1300 RKHD1 5.92 7.77
    1301 LRRK1 9.74 11.62 11.62 10.12
    1302 PTCH1 7.70 9.58
    1303 MGLL 7.30 9.18 9.18 10.57 9.18 8.06
    1304 YWHAH 8.94 10.82 10.82 9.09
    1305 PDE4D 6.78 8.66
    1306 MAF 8.05 9.95 9.95 8.25
    1307 PTGER3 5.18 7.09 7.09 6.06
    1308 PRKCD 9.49 11.40
    1309 CCDC64 8.15 10.07 10.07 7.55
    1310 RASL11A 7.89 6.65
    1311 KPNA2 11.18 13.09 13.09 11.78 13.09 11.55
    1312 GPR137B 8.65 10.58 10.58 9.36
    1313 TIAM1 6.97 8.90
    1314 TFDP1 10.95 12.90 12.90 10.49
    1315 SSBP2 10.47 12.42 12.42 10.32
    1316 REEP1 5.64 7.61
    1317 MAP2 7.85 9.83 9.83 7.75
    1318 HOXA9 5.15 7.12
    1319 SCRN1 11.81 9.54
    1320 LOC129607 8.79 10.78 10.78 9.33 10.78 9.45
    1321 SIAH2 10.35 12.34 12.34 10.57
    1322 DKFZP564O0823 6.96 8.95
    1323 POLQ 8.30 10.30 10.30 8.98 10.30 7.83
    1324 KLF15 5.88 7.88 7.88 9.36 7.88 6.74
    1325 PXDN 8.36 10.37
    1326 BTBD12 8.06 10.08 10.08 8.56
    1327 PHF6 11.19 13.21 13.21 11.96 13.21 12.09
    1328 SLC41A2 5.67 7.68
    1329 HN1 9.87 11.92 11.92 9.85 11.92 10.58
    1330 ZNF608 8.98 11.07 11.07 9.74
    1331 RNGTT 10.32 12.45
    1332 RAP2A 10.35 12.47
    1333 LIMK1 5.18 7.36 7.36 5.05
    1334 SMAD1 5.91 8.10 8.10 6.34
    1335 NCOA7 10.39 12.58
    1336 PRDM15 10.29 12.49
    1337 PELI1 10.67 12.88
    1338 PLS1 5.43 7.65 7.65 4.53
    1339 RAB23 6.14 8.36
    1340 NAP1L5 7.40 9.63 9.63 8.30 9.63 8.34
    1341 DNER 6.90 9.14
    1342 LRRC42 7.58 9.83
    1343 ID2 7.74 9.99
    1344 IBRDC2 9.98 12.24 12.24 8.84 12.24 9.94
    1345 DNMT1 11.21 13.50
    1346 STAC3 5.74 8.02 8.02 7.01
    1347 HMGB3 8.20 10.50 10.50 8.80 10.50 8.08
    1348 BMPR1A 6.75 9.06
    1349 SGK 10.06 12.37
    1350 CBX2 6.06 8.37 8.37 6.38
    1351 LRRC20 5.69 8.03
    1352 LRRC4 4.81 7.15 7.15 5.05
    1353 HOXA1 5.36 7.70
    1354 LRRC62 4.95 7.30
    1355 ATAD2 9.00 11.34 11.34 8.44 11.34 9.37
    1356 MOBKL1A 9.73 12.08 12.08 9.13 12.08 10.12
    1357 LOC220594 10.06 12.41 12.41 10.07
    1358 ZNF804A 6.14 8.51
    1359 C1orf113 5.99 8.36 8.36 5.74
    1360 FMNL2 6.58 8.96
    1361 H2AFX 12.49 10.60
    1362 ATP1B1 5.60 8.03
    1363 GPT2 6.54 8.97
    1364 PSRC1 9.89 7.46
    1365 SLC25A35 5.23 7.68
    1366 LHFPL2 8.94 11.41
    1367 UBE2J1 11.34 13.81 13.81 12.22
    1368 TBC1D8B 5.43 7.91 7.91 6.89
    1369 SGPP1 10.96 13.46 13.46 11.28
    1370 C11orf9 4.74 7.24
    1371 BCL6 12.29 14.82 14.82 10.60 14.82 11.78
    1372 ANUBL1 8.12 10.66 10.66 8.78
    1373 MTA3 8.37 10.92
    1374 PGBD5 4.87 7.45 7.45 5.87
    1375 LPP 11.00 13.59 13.59 10.07 13.59 10.89
    1376 NDFIP2 7.39 9.99
    1377 STMN1 11.76 9.03
    1378 PITPNC1 8.77 11.42 11.42 10.00
    1379 SH3RF1 7.37 10.05 10.05 8.10
    1380 ASF1B 8.56 11.25 11.25 7.91 11.25 8.27
    1381 FLJ20186 12.06 14.82 14.82 12.05
    1382 SLC16A2 8.08 5.17
    1383 PEX5 9.12 11.90 11.90 9.50
    1384 ECT2 7.45 10.23 10.23 7.70 10.23 7.63
    1385 MAML3 8.05 10.85
    1386 TEAD1 4.42 7.24
    1387 HMGB2 12.96 15.78 15.78 12.73 15.78 13.36
    1388 NCALD 5.15 7.97
    1389 RGC32 7.75 10.62
    1390 PPP1R3C 4.18 7.06
    1391 DEPDC1B 9.96 7.11
    1392 WEE1 10.11 13.01 13.01 10.32 13.01 11.84
    1393 FHL2 4.82 7.77
    1394 ITGB8 4.70 7.66
    1395 SLC1A1 10.86 8.88
    1396 FAM83D 7.36 10.32
    1397 UHRF1 12.22 8.72
    1398 C7orf41 4.94 7.95 7.95 6.29
    1399 ZBTB8 5.58 8.59 8.59 11.07
    1400 ZNF367 7.97 10.99 10.99 8.04 10.99 8.22
    1401 CDC25A 6.03 9.09 9.09 6.81
    1402 CHEK1 7.59 10.68 10.68 7.72
    1403 CDCA7 10.61 13.76 13.76 10.16 13.76 11.06
    1404 FGF13 4.55 7.69
    1405 SSBP3 6.20 9.35
    1406 EZH2 9.40 12.57 12.57 10.22
    1407 TNFSF11 5.18 8.36 8.36 5.91 8.36 9.78
    1408 PACSIN1 5.16 8.35
    1409 RRM2 10.59 13.82 13.82 9.47 13.82 10.79
    1410 POU4F1 5.62 8.85
    1411 MYBL2 9.07 12.41 12.41 9.12
    1412 KIAA1212 8.46 11.81 11.81 8.55
    1413 CCNE2 7.30 10.66 10.66 8.02 10.66 8.03
    1414 IGF2BP3 7.92 11.34 11.34 9.93 11.34 9.55
    1415 PRKAR2B 6.17 9.66 9.66 8.16
    1416 CADPS 5.04 8.58 8.58 6.18
    1417 ANKRD15 6.97 10.52 10.52 7.58
    1418 DAAM1 9.33 12.92
    1419 MAP1B 4.05 7.68 7.68 5.03 7.68 6.23
    1420 AFF2 6.32 10.00
    1421 E2F7 5.66 9.37 9.37 6.53 9.37 6.89
    1422 PRC1 8.37 12.08
    1423 ENPP5 3.54 7.26 7.26 4.97
    1424 E2F8 7.68 11.41
    1425 MED12L 7.82 11.59 11.59 7.46 11.59 10.57
    1426 LOC162073 6.30 10.08
    1427 LRRC32 4.14 7.93 7.93 6.61 7.93 4.95
    1428 DMXL2 6.57 10.38 10.38 6.61 10.38 7.76
    1429 FLJ20366 7.86 11.68 11.68 7.62 11.68 9.86
    1430 TOX 9.05 12.88 12.88 11.27
    1431 MME 11.56 10.33
    1432 FGD6 7.63 11.73 11.73 9.12
    1433 MYBL1 9.68 14.13 14.13 10.02 14.13 9.72
    *Empty cells indicate values not appreciably measured.
  • TABLE 16
    Predictor microRNAs that distinguish activated B-cell (ABC)
    DLBCL from germinal center B-cell (GCB) DLBC
    Higher
    ABC vs GCB in
    hsa-miR-93/mmu-miR-93/rno-miR-93 GCB
    hsa-miR-331-3p/mmu-miR-331-3p/rno-miR-331 GCB
    hsa-miR-129* GCB
    hsa-miR-423-3p/mmu-miR-423-3p/rno-miR-423 GCB
    hsa-miR-28-5p/mmu-miR-28/rno-miR-28 GCB
    mghv-miR-M1-7-3p GCB
    hsa-miR-518b GCB
    ebv-miR-BHRF1-1 GCB
    hsa-miR-140-5p/mmu-miR-140/rno-miR-140 GCB
    hsa-miR-505* GCB
    hsa-miR-675 GCB
    hsa-miR-198 GCB
    hsa-miR-125b-1*/mmu-miR-125b-3p/mo-miR- GCB
    125b-3p
    hsa-miR-361-5p/mmu-miR-361/rno-miR-361 GCB
    ebv-miR-BART8* GCB
  • TABLE 17
    Predictor microRNAs that distinguish activated B-cell (ABC)
    DLBCL from Burkitt lymphoma
    Higher
    ABC vs BL in
    hsa-miR-155 ABC
    hsa-miR-29c/mmu-miR- ABC
    29c/rno-miR-29c
    hsa-miR-146b-5p/mmu-miR- ABC
    146b/rno-miR-146b
    hsa-miR-29b/mmu-miR- ABC
    29b/rno-miR-29b
    hsa-miR-22/mmu-miR- ABC
    22/rno-miR-22
    hsa-miR-21/mmu-miR- ABC
    21/rno-miR-21
    hsa-miR-768-3p ABC
    hsa-miR-145/mmu-miR- ABC
    145/rno-miR-145
    hsa-miR-29a/mmu-miR- ABC
    29a/rno-miR-29a
    hsa-miR-30e/mmu-miR- ABC
    30e/rno-miR-30e
    hsa-miR-26a/mmu-miR- ABC
    26a/rno-miR-26a
    hsa-miR-101/mmu-miR- ABC
    101a/rno-miR-101a
    hsa-miR-24/mmu-miR- ABC
    24/rno-miR-24
    hsa-miR-26b/mmu-miR- ABC
    26b/rno-miR-26b
    hsa-miR-27a/mmu-miR- ABC
    27a/rno-miR-27a
    hsa-miR-27b/mmu-miR- ABC
    27b/rno-miR-27b
    hsa-miR-23b/mmu-miR- ABC
    23b/rno-miR-23b
    hsa-miR-23a/mmu-miR- ABC
    23a/rno-miR-23a
    hsa-miR-125b/mmu-miR- ABC
    125b-5p/rno-miR-125b-5p
    hsa-miR-30a/mmu-miR- ABC
    30a/rno-miR-30a
    hsa-miR-142-3p/mmu-miR- ABC
    142-3p/rno-miR-142-3p
    hsa-let-7a/mmu-let-7a/rno-let- ABC
    7a
    hsa-miR-30b/mmu-miR- ABC
    30b/rno-miR-30b-5p
    hsa-miR-142-5p/mmu-miR- ABC
    142-5p/rno-miR-142-5p
    hsa-miR-34b/mmu-miR-34b-3p ABC
    hsa-miR-16/mmu-miR-16/rno- ABC
    miR-16
    hsa-miR-30c/mmu-miR- ABC
    30c/rno-miR-30c
    hsa-let-7c/mmu-let-7c/rno-let- ABC
    7c
    hsa-miR-550 ABC
    hsa-miR-921 BL
    hsa-miR-30c-2*/mmu-miR- BL
    30c-2*/rno-miR-30c-2*
    hsa-miR-933 BL
    hsa-miR-658 BL
    hsa-miR-628-3p BL
    hsa-miR-503 BL
    hsa-miR-193a-5p BL
    hsa-miR-30b* BL
    hsa-miR-93/mmu-miR-93/rno- BL
    miR-93
    hsa-miR-18b BL
    hsa-miR-18a/mmu-miR- BL
    18a/rno-miR-18a
    hsa-miR-874/mmu-miR- BL
    874/rno-miR-874
  • TABLE 18
    Predictor microRNAs that distinguish activated B-cell (ABC)
    DLBCL from chronic lymphocytic leukemia
    Higher
    ABC vs CLL in
    hsa-miR-125b/mmu-miR- ABC
    125b-5p/rno-miR-125b-5p
    hsa-miR-126/mmu-miR- ABC
    126-3p/rno-miR-126
    hsa-miR-199a-3p/hsa- ABC
    miR-199b-3p/mmu-miR-
    199a-3p/mmu-miR-
    199b/rno-miR-199a-3p
    hsa-miR-145/mmu-miR- ABC
    145/rno-miR-145
    hsa-miR-143/mmu-miR- ABC
    143/rno-miR-143
    hsa-miR-637 ABC
    hsa-miR-371-5p ABC
    kshv-miR-K12-6-3p ABC
    hsa-miR-628-3p ABC
    hsa-miR-126*/mmu-miR- ABC
    126-5p/rno-miR-126*
    hsa-miR-193a-5p ABC
    hsa-miR-21/mmu-miR- ABC
    21/rno-miR-21
    hsa-miR-24/mmu-miR- ABC
    24/rno-miR-24
    hsa-miR-503 ABC
    hsa-miR-23a/mmu-miR- ABC
    23a/rno-miR-23a
    hsa-miR-23b/mmu-miR- ABC
    23b/rno-miR-23b
    hsa-miR-22/mmu-miR- ABC
    22/rno-miR-22
    hsa-miR-665 ABC
    hsa-let-7c/mmu-let-7c/rno- ABC
    let-7c
    hsa-miR-658 ABC
    hsa-let-7a/mmu-let-7a/rno- ABC
    let-7a
    mghv-miR-M1-4 ABC
    hsa-miR-933 ABC
    hsa-miR-550 CLL
    hsa-miR-30e/mmu-miR- CLL
    30e/rno-miR-30e
    hsa-miR-142- CLL
    5p/mmu-miR-142-
    5p/rno-miR-142-5p
    hsa-miR-101/mmu- CLL
    miR-101a/rno-miR-
    101a
    hsa-miR-185/mmu- CLL
    miR-185/rno-miR-185
    hsa-miR-888* CLL
    hsa-miR-199a- CLL
    5p/mmu-miR-199a-
    5p/rno-miR-199a-5p
    hsa-miR-668/mmu- CLL
    miR-668
    hsa-miR-549 CLL
    hsa-miR-801/mmu- CLL
    miR-801
    hsa-miR-649 CLL
    hsa-miR-625* CLL
    hsa-miR-140- CLL
    3p/mmu-miR-
    140*/rno-miR-140*
    hsa-let-7f/mmu-let- CLL
    7f/rno-let-7f
    hsa-miR-768-5p CLL
    hsa-miR-24-1*/mmu- CLL
    miR-24-1*/rno-miR-
    24-1*
    ebv-miR-BART13 CLL
    hsa-miR-339- CLL
    5p/mmu-miR-339-
    5p/rno-miR-339-5p
    hsa-miR-20b/mmu- CLL
    miR-20b/rno-miR-
    20b-5p
    hsa-miR-335/mmu- CLL
    miR-335-5p/rno-miR-
    335
    mghv-miR-M1-8 CLL
    hsa-miR-30d/mmu- CLL
    miR-30d/rno-miR-30d
    hsa-miR-363/mmu- CLL
    miR-363/rno-miR-363
    hsa-miR-361-3p CLL
    hsa-miR-107/mmu- CLL
    miR-107/rno-miR-107
    hsa-miR-154/mmu- CLL
    miR-154/rno-miR-154
    hsa-miR-638 CLL
    hsa-miR-340/mmu- CLL
    miR-340-5p/rno-miR-
    340-5p
    hsa-miR-331- CLL
    3p/mmu-miR-331-
    3p/rno-miR-331
    hsa-miR-151- CLL
    5p/mmu-miR-151-
    5p/rno-miR-151
    hsa-miR-636 CLL
    hsa-miR-33a/mmu- CLL
    miR-33/rno-miR-33
    hsa-miR-486- CLL
    5p/mmu-miR-486
    hsa-miR-150/mmu- CLL
    miR-150/rno-miR-
    150
    hsa-miR-25/mmu- CLL
    miR-25/rno-miR-25
    hsa-miR-331- CLL
    5p/mmu-miR-331-5p
    hsa-miR-299- CLL
    5p/mmu-miR-
    299*/rno-miR-299
    hsa-miR-891a CLL
    hsa-miR-144* CLL
    hsa-miR-363*/rno- CLL
    miR-363*
    hsa-miR-93/mmu- CLL
    miR-93/rno-miR-93
    hsa-miR-423- CLL
    3p/mmu-miR-423-
    3p/rno-miR-423
    hsa-let-7g/mmu-let- CLL
    7g
    hsa-miR-28-5p/mmu- CLL
    miR-28/rno-miR-28
    hsa-miR-20b* CLL
    hsa-miR-140- CLL
    5p/mmu-miR-
    140/rno-miR-140
    hsa-miR-519d CLL
    hsa-miR-147 CLL
    hsa-miR-487b/mmu- CLL
    miR-487b/rno-miR-
    487b
    hsa-miR-361- CLL
    5p/mmu-miR-
    361/rno-miR-361
    hsa-miR-186/mmu- CLL
    miR-186/rno-miR-
    186
    hsa-miR-32/mmu- CLL
    miR-32/rno-miR-32
    hsa-miR-129* CLL
    hsa-miR-30e*/mmu- CLL
    miR-30e*/rno-miR-
    30e*
    hsa-miR-196a*/mmu- CLL
    miR-196a*/rno-miR-
    196a*
  • TABLE 19
    Predictor microRNAs that distinguish activated B-cell (ABC)
    DLBCL from follicular lymphoma
    Higher
    ABC vs FL in
    hsa-miR-938 ABC
    hsa-miR-183*/mmu-miR- ABC
    183*
    hsa-miR-197/mmu-miR- ABC
    197
    hsa-miR-382/mmu-miR- ABC
    382/rno-miR-382
    hsa-miR-20b* ABC
    hsa-miR-524-5p ABC
    hsa-miR-337-3p ABC
    hsa-miR-600 ABC
    hsa-miR-96/mmu-miR- ABC
    96/rno-miR-96
    mghv-miR-M1-8 ABC
    hsa-miR-29c*/mmu-miR- ABC
    29c*/rno-miR-29c*
    hsa-miR-575 ABC
    hsa-miR-518a-3p ABC
    hsa-miR-361-5p/mmu-miR- ABC
    361/rno-miR-361
    hsa-miR-193b* ABC
    hsa-miR-340*/mmu-miR- ABC
    340-3p/rno-miR-340-3p
    hsa-miR-708/mmu-miR- ABC
    708/rno-miR-708
    hsa-miR-129* ABC
    hsa-miR-525-5p ABC
    hsa-miR-497/mmu-miR- FL
    497/rno-miR-497
    hsa-miR-22*/mmu-miR- FL
    22*/rno-miR-22*
    hsa-miR-130b/mmu-miR- FL
    130b/rno-miR-130b
    hsa-miR-551b* FL
    hsa-miR-331-3p/mmu-miR- FL
    331-3p/rno-miR-331
    ebv-miR-BART13 FL
    hsa-miR-877/mmu-miR- FL
    877/rno-miR-877
    hsa-miR-636 FL
    hsa-miR-922 FL
    hsa-miR-198 FL
    hsa-miR-342-5p/mmu-miR- FL
    342-5p/rno-miR-342-5p
    hsa-miR-585 FL
    ebv-miR-BART8* FL
    hsa-miR-617 FL
    hsa-miR-221* FL
    hsa-miR-125b-1*/mmu- FL
    miR-125b-3p/rno-miR-
    125b-3p
    hsa-miR-93/mmu-miR- FL
    93/rno-miR-93
    hsa-miR-363*/rno-miR- FL
    363*
    hsa-miR-744/mmu-miR- FL
    744
    hsa-miR-659 FL
    hsa-miR-490-3p/mmu-miR- FL
    490
    hsa-let-7d/mmu-let-7d/rno- FL
    let-7d
    hsa-miR-361-3p FL
    ebv-miR-BHRF1-1 FL
    hsa-miR-92b/mmu-miR- FL
    92b/rno-miR-92b
    hsa-miR-151-5p/mmu-miR- FL
    151-5p/rno-miR-151
    hsa-miR-144* FL
    hsa-miR-425/mmu-miR- FL
    425/rno-miR-425
    hsa-miR-138/mmu-miR- FL
    138/rno-miR-138
    hsa-miR-92a/mmu-miR- FL
    92a/rno-miR-92a
    hsa-miR-151-3p FL
    hsa-miR-25/mmu-miR- FL
    25/rno-miR-25
    hsa-miR-509-3-5p FL
    hsa-miR-30e*/mmu-miR- FL
    30e*/rno-rniR-30e*
    hsa-miR-28-5p/mmu-miR- FL
    28/rno-miR-28
    hsa-miR-200b*/mmu-miR- FL
    200b*
    hsa-miR-148b/mmu-miR- FL
    148b/rno-miR-148b-3p
    hsa-miR-488 FL
    hsa-miR-99b/mmu-miR- FL
    99b/rno-miR-99b
    hsa-miR-339-5p/mmu-miR- FL
    339-5p/rno-miR-339-5p
    hsv1-miR-H1 FL
    hsa-miR-32/mmu-miR- FL
    32/rno-miR-32
    hsa-miR-885-5p FL
    hsa-miR-630 FL
    ebv-miR-BART16 FL
    hsa-miR-505* FL
    hsa-miR-374b* FL
    hsa-miR-574-3p/mmu-miR- FL
    574-3p
    hsa-miR-874/mmu-miR- FL
    874/rno-miR-874
    hsa-miR-423-3p/mmu-miR- FL
    423-3p/rno-miR-423
    hsa-miR-889 FL
    hcmv-miR-UL148D FL
    hsa-miR-487b/mmu-miR- FL
    487b/rno-miR-487b
    hsa-miR-552 FL
    hsa-miR-220b FL
    hsa-miR-551a FL
    hsa-let-7d*/mmu-let- FL
    7d*/rno-let-7d*
    kshv-miR-K12-5 FL
    hsa-miR-629* FL
    hsa-miR-99b*/mmu-miR- FL
    99b*/rno-miR-99b*
    hsa-miR-615-3p/mmu-miR- FL
    615-3p
    hsa-miR-657 FL
    hsa-miR-301a/mmu-miR- FL
    301a/rno-miR-301a
    hsa-miR-518b FL
    hsa-miR-194/mmu- FL
    miR-194/rno-miR-
    194
    hsa-miR-647 FL
    kshv-miR-K12-6-5p FL
    hsa-miR-622 FL
    hsa-miR-516b FL
    hsa-miR-675 FL
    hsa-miR-526b FL
    hsa-miR-671- FL
    5p/mmu-miR-671-5p
    hsa-miR-18a/mmu- FL
    miR-18a/rno-miR-
    18a
    hsa-miR-18b FL
    hsa-miR-181b/mmu- FL
    miR-181b/rno-miR-
    181b
    hsa-miR-215 FL
    hsa-miR-153/mmu- FL
    miR-153/rno-miR-
    153
    hsa-miR-625 FL
    hsa-miR-510 FL
    hsa-miR-519d FL
    mghv-miR-M1-7-3p FL
    hsa-miR-485- FL
    3p/mmu-miR-485*
    hsa-miR-483-5p FL
    hsa-miR-140- FL
    5p/mmu-miR-
    140/rno-miR-140
    hsa-miR-921 FL
    hsa-miR-186/mmu- FL
    miR-186/rno-miR-
    186
    hsa-miR-196a*/mmu- FL
    miR-196a*/rno-miR-
    196a*
    hsa-miR-381/mmu- FL
    miR-381/rno-miR-
    381
    hsa-miR-620 FL
    hsa-miR-152/mmu- FL
    miR-152/rno-miR-
    152
    hsa-miR-766 FL
    mghv-miR-M1-7-5p FL
    hsa-miR-374b/mmu- FL
    miR-374/rno-miR-
    374
    hsa-let-7c/mmu-let- FL
    7c/rno-let-7c
    kshv-miR-K12-8 FL
    mghv-miR-M1-3 FL
    hsa-miR-920 FL
    hsa-miR-519e* FL
    hsa-miR-147 FL
    hsa-miR-424 FL
    hsa-miR-193b FL
    ebv-miR-BART19-3p FL
    hsa-miR-146b-3p FL
    hsa-miR-30c/mmu- FL
    miR-30c/rno-miR-
    30c
    hsa-miR-30a/mmu- FL
    miR-30a/rno-miR-
    30a
    hsa-miR-939 FL
    hsa-let-7a/mmu-let- FL
    7a/rno-let-7a
    hsa-miR-122* FL
    hsa-miR-206/mmu- FL
    miR-206/rno-miR-
    206
    ebv-miR-BART18-3p FL
    hsa-miR-183/mmu- FL
    miR-183/rno-miR-
    183
    hsa-miR-9*/mmu- FL
    miR-9*/rno-miR-9*
    kshv-miR-K12-1 FL
    hsa-miR-34c- FL
    5p/mmu-miR-
    34c/rno-miR-34c
    hsa-miR-934 FL
    hsa-miR-890 FL
    hsa-miR-514 FL
    hsa-miR-297/mmu- FL
    miR-297a
    hsa-miR-553 FL
    hsa-miR-765 FL
    hsa-let-7b*/mmu-let- FL
    7b*/rno-let-7b*
    hsa-miR-500* FL
    hsa-miR-601 FL
    ebv-miR-BHRF1-3 FL
    hsa-miR-296- FL
    3p/mmu-miR-296-
    3p/rno-miR-296
    hsa-miR-574- FL
    5p/mmu-miR-574-5p
    hsa-miR-409- FL
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    hsa-miR-195* FL
    hsa-miR-635 FL
    hsa-miR-542- FL
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    hcmv-miR-US25-1* FL
    mghv-miR-M1-2 FL
    hsa-miR-509-5p FL
    hsa-miR-340/mmu- FL
    miR-340-5p/rno-
    miR-340-5p
    hsa-miR-891a FL
    hsa-miR-23a/mmu- FL
    miR-23a/rno-miR-
    23a
    hsa-miR-19b/mmu- FL
    miR-19b/rno-miR-
    19b
    hsa-miR-515-5p FL
    hsa-miR-23b/mmu- FL
    miR-23b/rno-miR-
    23b
    hsa-miR-498 FL
    hsa-miR-886-5p FL
    hsa-miR-220c FL
    hsa-miR-10a/mmu- FL
    miR-10a/rno-miR-
    10a-5p
    hsa-miR-32* FL
    hsa-miR-24/mmu- FL
    miR-24/rno-miR-24
    hsa-miR-98/mmu- FL
    miR-98/rno-miR-98
    hsa-let-7g/mmu-let-7g FL
    hsa-miR-302a/mmu- FL
    miR-302a
    hsa-miR-625* FL
    hsa-miR-30b* FL
    hsa-miR-30b/mmu- FL
    miR-30b/rno-miR-
    30b-5p
    hsa-miR-377* FL
    hsa-miR-106b*/mmu- FL
    miR-106b*/rno-miR-
    106b*
    hsa-miR-181a-2* FL
    hsa-miR-887 FL
    hsa-miR-208a/mmu- FL
    miR-208a/rno-miR-
    208
    ebv-miR-BART7* FL
    hsa-miR-7-2* FL
    hsa-miR-155* FL
    hsa-miR-513a-3p FL
    kshv-miR-K12-7 FL
    hsa-miR-299-3p FL
    hsa-miR-218-2*/mmu- FL
    miR-218-2*/rno-miR-
    218*
    hsa-miR-130b*/mmu- FL
    miR-130b*
    hsa-miR-620 FL
    hsa-miR-33a/mmu- FL
    miR-33/rno-miR-33
    hsa-miR-7/mmu-miR- FL
    7a/rno-miR-7a
    ebv-miR-BART6-3p FL
    hsa-miR-22/mmu- FL
    miR-22/rno-miR-22
    hsa-miR-199b-5p FL
    hsa-miR-768-3p FL
    hsa-miR-494/mmu- FL
    miR-494/rno-miR-494
    hsa-miR-602 FL
    hsa-miR-125b-2*/rno- FL
    miR-125b*
    hsa-miR-300 FL
    hsa-let-7e/mmu-let- FL
    7e/rno-let-7e
    hsa-miR-298 FL
    hsa-miR-576-3p FL
    hsa-miR-187* FL
    hsa-miR-365/mmu- FL
    miR-365/rno-miR-365
    hsa-miR-518a-5p/hsa- FL
    miR-527
    hsa-miR-302d* FL
    hsa-miR-105 FL
    hsa-miR-126/mmu- FL
    miR-126-3p/rno-miR-
    126
    hsa-miR-107/mmu- FL
    miR-107/rno-miR-107
    hsa-miR-299-5p/mmu- FL
    miR-299*/rno-miR-
    299
    hsa-miR-28-3p/rno- FL
    miR-28*
    hsa-miR-21/mmu- FL
    miR-21/rno-miR-21
    hsa-miR-27b/mmu- FL
    miR-27b/rno-miR-27b
    hsa-miR-516a-5p FL
    hsa-miR-129-5p/mmu- FL
    miR-129-5p/rno-miR-
    129
    hsa-miR-583 FL
    hsa-miR-483-3p FL
    hsa-miR-326/mmu- FL
    miR-326/rno-miR-326
    hsa-miR-548d-5p FL
    hsa-miR-629 FL
    ebv-miR-BART5 FL
    hsa-miR-665 FL
    hsa-miR-493 FL
    hsa-miR-484/mmu- FL
    miR-484/rno-miR-484
    hsa-miR-645 FL
    hsa-miR-452 FL
    hsa-miR-518c* FL
    hsa-miR-24-2*/mmu- FL
    miR-24-2*/rno-miR-
    24-2*
    hsa-miR-124/mmu- FL
    miR-124/rno-miR-124
    hsa-miR-184/mmu- FL
    miR-184/rno-miR-184
    hsa-miR-27a*/mmu- FL
    miR-27a*/rno-miR-
    27a*
    hsa-miR-25* FL
    hsa-miR-34b/mmu- FL
    miR-34b-3p
    ebv-miR-BART17-5p FL
    hsa-miR-658 FL
    hsa-miR-212/mmu- FL
    miR-212/rno-miR-212
    hsa-miR-99a/mmu- FL
    miR-99a/rno-miR-99a
    hsa-miR-801/mmu- FL
    miR-801
    hsa-miR-491-3p FL
    hsa-miR-551b/mmu- FL
    miR-551b/rno-miR-
    551b
    hsa-miR-214/mmu- FL
    miR-214/rno-miR-214
    hsa-miR-30e/mmu- FL
    miR-30e/rno-miR-30e
    hsa-miR-888* FL
    hsa-miR-505/rno-miR- FL
    505
    hsa-miR-27a/mmu- FL
    miR-27a/rno-miR-27a
    hsa-miR-15a/mmu- FL
    miR-15a
    hsa-miR-20a/mmu- FL
    miR-20a/rno-miR-20a
    kshv-miR-K12-3 FL
    hsa-miR-455-3p FL
    hsa-miR-486-5p/mmu- FL
    miR-486
  • TABLE 20
    Predictor microRNAs that distinguish activated B-cell (ABC)
    DLBCL from Hodgkin's lymphoma
    Higher
    ABC vs HL in
    hsa-miR-19b/mmu-miR- ABC
    19b/rno-miR-19b
    hsa-miR-30b/mmu-miR- ABC
    30b/rno-miR-30b-5p
    hsa-miR-142-3p/mmu- ABC
    miR-142-3p/rno-miR-142-
    3p
    hsa-miR-768-3p ABC
    hsa-miR-30c/mmu-miR- ABC
    30c/rno-miR-30c
    hsa-miR-29b/mmu-miR- ABC
    29b/rno-miR-29b
    hsa-miR-24/mmu-miR- ABC
    24/rno-miR-24
    hsa-miR-22/mmu-miR- ABC
    22/rno-miR-22
    hsa-miR-30e/mmu-miR- ABC
    30e/rno-miR-30e
    hsa-miR-30a/mmu-miR- ABC
    30a/rno-miR-30a
    hsa-miR-26b/mmu-miR- ABC
    26b/rno-miR-26b
    hsa-miR-26a/mmu-miR- ABC
    26a/rno-miR-26a
    hsa-miR-15a/mmu-miR- ABC
    15a
    hsa-miR-16/mmu-miR- ABC
    16/rno-miR-16
    hsa-miR-142-5p/mmu- ABC
    miR-142-5p/rno-miR-142-
    5p
    hsa-miR-29a/mmu-miR- ABC
    29a/rno-miR-29a
    hsa-miR-101/mmu-miR- ABC
    101a/rno-miR-101a
    hsa-miR-126/mmu-miR- ABC
    126-3p/rno-miR-126
    hsa-miR-451/mmu-miR- ABC
    451/rno-miR-451
    hsa-let-7a/mmu-let-7a/rno- ABC
    let-7a
    hsa-miR-23b/mmu-miR- ABC
    23b/rno-miR-23b
    hsa-miR-21/mmu-miR- ABC
    21/rno-miR-21
    hsa-miR-29c/mmu-miR- ABC
    29c/rno-miR-29c
    hsa-miR-20a/mmu-miR- ABC
    20a/rno-miR-20a
    hsa-miR-27b/mmu-miR- ABC
    27b/rno-miR-27b
    hsa-miR-23a/mmu-miR- ABC
    23a/rno-miR-23a
    hsa-miR-27a/mmu-miR- ABC
    27a/rno-miR-27a
    hsa-miR-550 ABC
    hsa-let-7c/mmu-let-7c/rno- ABC
    let-7c
    hsa-miR-34b/mmu-miR- ABC
    34b-3p
    hsa-miR-933 HL
    hsa-miR-30c-2*/mmu- HL
    miR-30c-2*/rno-miR-30c-
    2*
    hsa-miR-503 HL
    hsa-miR-765 HL
    hsa-miR-658 HL
    hsa-miR-620 HL
    hsa-miR-921 HL
    hsa-miR-30b* HL
    mghv-miR-M1-4 HL
    hsa-miR-939 HL
    hsa-miR-494/mmu-miR- HL
    494/rno-miR-494
    hsa-miR-32* HL
    hsa-miR-491-3p HL
    hsa-miR-10a/mmu-miR- HL
    10a/rno-miR-10a-5p
    hsa-miR-33a/mmu-miR- HL
    33/rno-miR-33
    hsa-miR-99a/mmu-miR- HL
    99a/rno-miR-99a
    hsa-miR-199b-5p HL
    hsa-miR-365/mmu-miR- HL
    365/rno-miR-365
    hsa-miR-520d-5p HL
    hsa-miR-518c* HL
    hsa-miR-32/mmu-miR- HL
    32/rno-miR-32
    hsa-miR-214/mmu-miR- HL
    214/rno-miR-214
    hsa-miR-98/mmu-miR- HL
    98/rno-miR-98
    hsa-miR-302d* HL
    hsa-miR-30e*/mmu-miR- HL
    30e*/rno-miR-30e*
    hsa-miR-374b/mmu-miR- HL
    374/rno-miR-374
    hsa-miR-29a*/mmu-miR- HL
    29a*/rno-miR-29a*
    hsa-miR-532-5p/mmu- HL
    miR-532-5p/rno-miR-532-
    5p
    hsa-miR-149* HL
    hsa-miR-422a HL
    ebv-miR-BHRF1-2 HL
    hsa-miR-634 HL
    hsa-miR-143* HL
    hsa-miR-620 HL
    hsa-miR-660 HL
    hsa-miR-140-5p/mmu- HL
    miR-140/rno-miR-140
    hsa-miR-28-5p/mmu-miR- HL
    28/rno-miR-28
    hsa-miR-519c-5p/hsa- HL
    miR-519b-5p/hsa-miR-
    523*/hsa-miR-518e*/hsa-
    miR-522*/hsa-miR-519a*
    hsa-miR-505/rno-miR-505 HL
    hsa-miR-184/mmu-miR- HL
    184/rno-miR-184
    hsa-miR-107/mmu-miR- HL
    107/rno-miR-107
    hsa-miR-298 HL
    hsa-miR-455-3p HL
    hsa-miR-638 HL
    hsa-miR-502-3p HL
    hsa-miR-149/mmu-miR- HL
    149
    hsa-miR-583 HL
    hsa-miR-105 HL
    hsa-miR-128/mmu-miR- HL
    128/rno-miR-128
    hsa-miR-656 HL
    hsa-miR-497/mmu-miR- HL
    497/rno-miR-497
    hsa-miR-152/mmu-miR- HL
    152/rno-miR-152
    hsa-miR-151-5p/mmu- HL
    miR-151-5p/rno-miR-151
    hsa-miR-148b/mmu-miR- HL
    148b/rno-miR-148b-3p
    hsa-miR-300 HL
    hsa-miR-144* HL
    hsa-miR-145*/mmu-miR- HL
    145*
    hcmv-miR-UL70-3p HL
    hsa-miR-28-3p/rno-miR- HL
    28*
    hsa-miR-27a*/mmu-miR- HL
    27a*/rno-miR-27a*
    hsa-miR-194/mmu-miR- HL
    194/rno-miR-194
    hsa-miR-130b*/mmu-miR- HL
    130b*
    hsa-miR-548d-5p HL
    hsa-miR-937 HL
    hsa-miR-7/mmu-miR- HL
    7a/rno-miR-7a
    hsa-miR-518a-5p/hsa- HL
    miR-527
    hsa-miR-323-3p/mmu- HL
    miR-323-3p/rno-miR-323
    hsa-miR-215 HL
    hsa-miR-513a-3p HL
    hsa-miR-595 HL
    hsa-miR-515-5p HL
    hsa-miR-483-3p HL
    hsa-miR-330-5p/mmu- HL
    miR-330/rno-miR-330
    hsa-miR-18b HL
    hsa-miR-509-3p HL
    hsa-miR-151-3p HL
    hsa-miR-934 HL
    hsa-miR-328/mmu-miR- HL
    328/rno-miR-328
    hsa-miR-187* HL
    kshv-miR-K12-3 HL
    hsa-miR-373* HL
    hsa-miR-96/mmu-miR- HL
    96/rno-miR-96
    hsa-miR-186/mmu-miR- HL
    186/rno-miR-186
    hsa-miR-886-5p HL
    hsa-miR-424 HL
    hsa-miR-147 HL
    hsa-miR-340/mmu-miR- HL
    340-5p/rno-miR-340-5p
    hsa-miR-129-5p/mmu- HL
    miR-129-5p/rno-miR-129
    hsa-miR-25* HL
    hsa-miR-193b HL
    hsa-miR-574-5p/mmu- HL
    miR-574-5p
    hsa-miR-589 HL
    hsa-miR-339-5p/mmu- HL
    miR-339-5p/rno-miR-
    339-5p
    hsa-miR-34c-5p/mmu- HL
    miR-34c/rno-miR-34c
    hsa-miR-891a HL
    hsa-miR-18a/mmu-miR- HL
    18a/rno-miR-18a
    hsa-miR-196a*/mmu- HL
    miR-196a*/rno-miR-
    196a*
    hsa-miR-17*/rno-miR- HL
    17-3p
    hsa-miR-296-5p/mmu- HL
    miR-296-5p/rno-miR-
    296*
    hsa-miR-25/mmu-miR- HL
    25/rno-miR-25
    hsa-miR-509-5p HL
    hsa-miR-550* HL
    hsa-miR-708/mmu-miR- HL
    708/rno-miR-708
    hsa-miR-146b-3p HL
    hsa-miR-625* HL
    hsa-miR-210/mmu-miR- HL
    210/rno-miR-210
    hsa-miR-93/mmu-miR- HL
    93/rno-miR-93
    hsa-miR-548b-3p HL
    hsa-miR-652/mmu-miR- HL
    652/rno-miR-652
    hsa-miR-153/mmu-miR- HL
    153/rno-miR-153
    mghv-miR-M1-3 HL
    hsa-miR-194* HL
    hsa-miR-23a*/rno-miR- HL
    23a*
    hsa-miR-943 HL
    hsa-let-7d/mmu-let- HL
    7d/rno-let-7d
    hsa-miR-498 HL
    hsa-miR-381/mmu-miR- HL
    381/rno-miR-381
    hsa-miR-586 HL
    hsa-miR-137/mmu-miR- HL
    137/rno-miR-137
    hsa-miR-610 HL
    hsa-miR-920 HL
    hsa-miR-936 HL
    hsa-miR-744/mmu-miR- HL
    744
    ebv-miR-BART5 HL
    hsa-miR-21* HL
    hsa-miR-516a-5p HL
    hsa-miR-576-5p HL
    mghv-miR-M1-6 HL
    hsa-miR-425/mmu-miR- HL
    425/rno-miR-425
    hsa-miR-220c HL
    hsa-miR-10a*/mmu-miR- HL
    10a*/rno-miR-10a-3p
    hsa-miR-452 HL
    hsa-miR-345 HL
    hsa-miR-29c*/mmu-miR- HL
    29c*/rno-miR-29c*
    hsa-miR-887 HL
    hsa-miR-7-2* HL
    hsa-miR-363*/rno-miR- HL
    363*
    hsa-miR-22*/mmu-miR- HL
    22*/rno-miR-22*
    hsa-miR-922 HL
    hsa-miR-92b* HL
    hsa-miR-526a/hsa-miR- HL
    520c-5p/hsa-miR-518d-
    5p
    hsa-miR-574-3p/mmu- HL
    miR-574-3p
    hsa-miR-92a/mmu-miR- HL
    92a/rno-miR-92a
    hsa-miR-423-3p/mmu- HL
    miR-423-3p/rno-miR-423
    hsa-miR-526b HL
    hsa-miR-526b* HL
    ebv-miR-BART6-3p HL
    hsa-miR-92b/mmu-miR- HL
    92b/rno-miR-92b
    hsa-miR-519e* HL
    hiv1-miR-H1 HL
    hsa-miR-623 HL
    hsa-miR-483-5p HL
    mghv-miR-M1-2 HL
    mghv-miR-M1-7-3p HL
    hsa-miR-519e HL
    hsa-miR-361-5p/mmu- HL
    miR-361/rno-miR-361
    hsa-miR-650 HL
    hsa-miR-361-3p HL
    hsa-miR-374b* HL
    kshv-miR-K12-8 HL
    hsa-miR-150*/mmu-miR- HL
    150*
    hsa-miR-425*/mmu-miR- HL
    425*
    hsa-miR-135a*/mmu- HL
    miR-135a*
    hsa-miR-612 HL
    hsa-miR-212/mmu-miR- HL
    212/rno-miR-212
    hsa-miR-125b-2*/rno- HL
    miR-125b*
    hcmv-miR-UL112 HL
    hsa-miR-500 HL
    hsa-miR-502-5p HL
    ebv-miR-BART18-3p HL
    hsa-miR-625 HL
    hsa-miR-138/mmu-miR- HL
    138/rno-miR-138
    hsa-miR-500* HL
    hsa-miR-124*/mmu-miR- HL
    124*/rno-miR-124*
    hsa-miR-516b HL
    hsa-miR-30c-1*/mmu- HL
    miR-30c-1*/rno-miR-
    30c-1*
    hsa-miR-331-5p/mmu- HL
    miR-331-5p
    hsa-miR-510 HL
    hsa-miR-376a* HL
    hsa-miR-640 HL
    hsa-miR-331-3p/mmu- HL
    miR-331-3p/rno-miR-331
    hsa-miR-602 HL
    hsa-miR-485-3p/mmu- HL
    miR-485*
    hsa-miR-488 HL
    hsa-miR-125a- HL
    3p/mmu-miR-125a-
    3p/rno-miR-125a-3p
    hsa-miR-24-2*/mmu- HL
    miR-24-2*/rno-miR-
    24-2*
    hsa-miR-484/mmu- HL
    miR-484/rno-miR-
    484
    hsa-miR-106b*/mmu- HL
    miR-106b*/rno-miR-
    106b*
    hsa-miR-600 HL
    hsa-let-7b*/mmu-let- HL
    7b*/rno-let-7b*
    hsa-miR-302c* HL
    hsa-miR-20b* HL
    hsa-miR-524-5p HL
    hsa-miR-505* HL
    hsa-miR-542- HL
    5p/mmu-miR-542-
    5p/rno-miR-542-5p
    hsa-miR-557 HL
    hsa-miR-183/mmu- HL
    miR-183/rno-miR-
    183
    hsa-miR-122* HL
    hsa-miR-675 HL
    hsv1-miR-H1 HL
    hsa-miR-99b/mmu- HL
    miR-99b/rno-miR-
    99b
    hsa-miR-766 HL
    hsa-miR-409- HL
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    ebv-miR-BART20-3p HL
    hsa-miR-129* HL
    mghv-miR-M1-7-5p HL
    hsa-miR-671- HL
    5p/mmu-miR-671-5p
    hsa-miR-629 HL
    hsa-miR-553 HL
    hsa-let-7d*/mmu-let- HL
    7d*/rno-let-7d*
    hsa-miR-601 HL
    hsa-miR-645 HL
    hsa-miR-221* HL
    hsa-miR-874/mmu- HL
    miR-874/rno-miR-
    874
    hsa-miR-890 HL
    hsa-miR-492 HL
    hsa-miR-629* HL
    hsa-miR-635 HL
    hsa-miR-130b/mmu- HL
    miR-130b/rno-miR-
    130b
    hsa-miR-197/mmu- HL
    miR-197
    hsa-miR-654-5p HL
    hsa-miR-518b HL
    hsa-miR-889 HL
    hsa-miR-584 HL
    hsa-miR-198 HL
    hsa-miR-636 HL
    hsa-miR-630 HL
    hsa-miR-490-5p HL
    hsa-miR-663 HL
    hcmv-miR-UL148D HL
    hsa-miR-337-3p HL
    hsa-miR-9*/mmu- HL
    miR-9*/rno-miR-9*
    hsa-miR-200b*/mmu- HL
    miR-200b*
    ebv-miR-BART9* HL
    hsa-miR-342- HL
    5p/mmu-miR-342-
    5p/rno-miR-342-5p
    hsa-miR-206/mmu- HL
    miR-206/rno-miR-
    206
    hcmv-miR-US25-1* HL
    hsa-miR-659 HL
    hsa-miR-514 HL
    kshv-miR-K12-6-5p HL
    hsa-miR-508-5p HL
    hsa-miR-377* HL
    ebv-miR-BART16 HL
    hsa-miR-181b/mmu- HL
    miR-181b/rno-miR-
    181b
    hsa-miR-622 HL
    kshv-miR-K12-1 HL
    hsa-miR-490- HL
    3p/mmu-miR-490
    hsa-miR-125b- HL
    1*/mmu-miR-125b-
    3p/rno-miR-125b-3p
    hsa-miR-124/mmu- HL
    miR-124/rno-miR-
    124
    hsa-miR-657 HL
    ebv-miR-BHRF1-3 HL
    kshv-miR-K12-5 HL
    hsa-miR-487b/mmu- HL
    miR-487b/rno-miR-
    487b
    hsa-miR-183*/mmu- HL
    miR-183*
    hsa-miR-297/mmu- HL
    miR-297a
    hsa-miR-885-5p HL
    hsa-miR-296- HL
    3p/mmu-miR-296-
    3p/rno-miR-296
    ebv-miR-BART19-3p HL
    hsa-miR-617 HL
    hsa-miR-519d HL
    hsa-miR-195* HL
    hsa-miR-575 HL
    hsa-miR-208a/mmu- HL
    miR-208a/rno-miR-
    208
    hsa-miR-647 HL
    hsa-miR-525-5p HL
    ebv-miR-BART8* HL
    hsa-miR-340*/mmu- HL
    miR-340-3p/rno-miR-
    340-3p
    hsa-miR-220b HL
    hsa-miR-382/mmu- HL
    miR-382/rno-miR-
    382
    hsa-miR-585 HL
    hsa-miR-877/mmu- HL
    miR-877/rno-miR-
    877
    hsa-miR-99b*/mmu- HL
    miR-99b*/rno-miR-
    99b*
    ebv-miR-BHRF1-1 HL
    hsa-miR-326/mmu- HL
    miR-326/rno-miR-
    326
    ebv-miR-BART7* HL
    hsa-miR-615- HL
    3p/mmu-miR-615-3p
    mghv-miR-M1-8 HL
    hsa-miR-193b* HL
    ebv-miR-BART13 HL
    hsa-miR-433/mmu- HL
    miR-433/rno-miR-
    433
    hsa-miR-202 HL
    hsa-miR-551b* HL
    hsa-miR-551a HL
    hsa-miR-542- HL
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    hsa-miR-338- HL
    5p/mmu-miR-338-
    5p/rno-miR-338*
    hsa-miR-299-3p HL
    hsa-miR-518a-3p HL
    hsa-miR-181a-2* HL
    hsa-miR-938 HL
    hsa-miR-509-3-5p HL
    hsa-miR-552 HL
  • TABLE 21
    Predictor microRNAs that distinguish germinal center B-cell like
    (GCB) DLBCL from Burkitt lymphoma
    GCBvsBL Higher in
    hsa-miR-129* GCB
    hsa-miR-28-5p/mmu-miR-28/rno- GCB
    miR-28
    hsa-miR-155 GCB
    hsa-miR-196a*/mmu-miR-196a*/rno- GCB
    miR-196a*
    hsa-miR-146a/mmu-miR-146a/rno- GCB
    miR-146a
    hsa-miR-331-3p/mmu-miR-331- GCB
    3p/rno-miR-331
    hsa-miR-215 GCB
    hsa-miR-600 GCB
    mghv-miR-M1-7-3p GCB
    hsa-miR-107/mmu-miR-107/rno- GCB
    miR-107
    hsa-miR-886-3p GCB
    hsa-miR-140-5p/mmu-miR-140/rno- GCB
    miR-140
    hsa-miR-154/mmu-miR-154/rno- GCB
    miR-154
    hsa-miR-103/mmu-miR-103/rno- GCB
    miR-103
    hsa-let-7g/mmu-let-7g GCB
    hsa-miR-222/mmu-miR-222/rno- GCB
    miR-222
    hsa-miR-221/mmu-miR-221/rno- GCB
    miR-221
    hsa-miR-320/mmu-miR-320/rno- GCB
    miR-320
    hsa-miR-140-3p/mmu-miR-140*/rno- GCB
    miR-140*
    hsa-miR-148a/mmu-miR-148a GCB
    hsa-miR-365/mmu-miR-365/rno-miR- GCB
    365
    hsa-miR-29c/mmu-miR-29c/rno-miR- GCB
    29c
    hsa-miR-30d/mmu-miR-30d/rno-miR- GCB
    30d
    hsa-miR-214/mmu-miR-214/rno-miR- GCB
    214
    hsa-miR-146b-5p/mmu-miR-146b/rno- GCB
    miR-146b
    hsa-miR-342-3p/mmu-miR-342-3p/rno- GCB
    miR-342-3p
    hsa-miR-374a GCB
    hsa-miR-223/mmu-miR-223/rno-miR- GCB
    223
    hsa-miR-29b/mmu-miR-29b/rno-miR- GCB
    29b
    hsa-miR-21/mmu-miR-21/rno-miR-21 GCB
    hsa-miR-29a/mmu-miR-29a/rno-miR- GCB
    29a
    hsa-miR-23b/mmu-miR-23b/rno-miR- GCB
    23b
    hsa-miR-24/mmu-miR-24/rno-miR-24 GCB
    hsa-miR-26a/mmu-miR-26a/rno-miR- GCB
    26a
    hsa-miR-26b/mmu-miR-26b/rno-miR- GCB
    26b
    hsa-miR-34b/mmu-miR-34b-3p GCB
    hsa-miR-503 BL
    hsa-miR-30b* BL
  • TABLE 22
    Predictor microRNAs that distinguish germinal center B-cell like
    (GCB) DLBCL from chronic lymphocytic leukemia
    Higher
    GCB vs CLL in
    hsa-miR-181a/mmu- GCB
    miR-181a/rno-miR-
    181a
    hsa-miR-886-5p GCB
    mghv-miR-M1-7-3p GCB
    hsa-miR-934 GCB
    mghv-miR-M1-3 GCB
    hsa-miR-485- GCB
    3p/mmu-miR-485*
    hsa-miR-125b/mmu- GCB
    miR-125b-5p/rno-
    miR-125b-5p
    hsa-miR-637 GCB
    hsa-miR-365/mmu- GCB
    miR-365/rno-miR-
    365
    hsa-miR-505* GCB
    hsa-miR-199a- GCB
    3p/hsa-miR-199b-
    3p/mmu-miR-199a-
    3p/mmu-miR-
    199b/rno-miR-199a-
    3p
    hsa-miR-675 GCB
    hsa-miR-424 GCB
    ebv-miR-BHRF1-2 GCB
    hsa-miR-519c- GCB
    5p/hsa-miR-519b-
    5p/hsa-miR-
    523*/hsa-miR-
    518e*/hsa-miR-
    522*/hsa-miR-
    519a*
    hsa-miR-130a/mmu- GCB
    miR-130a/rno-miR-
    130a
    hsa-miR-943 GCB
    hsa-miR-126/mmu- GCB
    miR-126-3p/rno-
    miR-126
    hsa-miR-193b GCB
    hsa-miR-198 GCB
    hsa-miR- GCB
    200b*/mmu-miR-
    200b*
    kshv-miR-K12-6-3p GCB
    hsa-miR-220c GCB
    hsa-miR-374b* GCB
    hsa-miR-518b GCB
    hsa-miR-920 GCB
    hsa-miR-125b- GCB
    1*/mmu-miR-125b-
    3p/rno-miR-125b-3p
    ebv-miR-BART8* GCB
    ebv-miR-BART16 GCB
    hsa-miR-630 GCB
    hsa-miR-483-5p GCB
    hsa-miR-422a GCB
    hsa-miR-526b GCB
    hsa-miR-145/mmu- GCB
    miR-145/rno-miR-
    145
    hsa-miR-126*/mmu- GCB
    miR-126-5p/rno-
    miR-126*
    hsa-miR-143/mmu- GCB
    miR-143/rno-miR-
    143
    hsa-miR-100/mmu- GCB
    miR-100/rno-miR-100
    hsa-miR-371-5p GCB
    hsa-miR-193a-5p GCB
    hsa-miR-628-3p GCB
    hsa-miR-185* GCB
    hsa-miR-10b/mmu- GCB
    miR-10b/rno-miR-10b
    hsa-miR-665 GCB
    hsa-miR-503 GCB
    hsa-miR-642 GCB
    hsa-miR-658 GCB
    hsa-miR-21/mmu- GCB
    miR-21/rno-miR-21
    hsa-miR-23a/mmu- GCB
    miR-23a/rno-miR-23a
    hsa-miR-125a- GCB
    5p/mmu-miR-125a-
    5p/rno-miR-125a-5p
    hsa-miR-24/mmu- GCB
    miR-24/rno-miR-24
    hsa-miR-23b/mmu- GCB
    miR-23b/rno-miR-23b
    hsa-miR-620 GCB
    hsa-miR-933 GCB
    hsa-miR-30b* GCB
    hsa-miR-22/mmu- GCB
    miR-22/rno-miR-22
    hsa-let-7e/mmu-let- GCB
    7e/rno-let-7e
    mghv-miR-M1-4 GCB
    hsa-miR-149* GCB
    hsa-miR-765 GCB
    hsa-let-7c/mmu-let- GCB
    7c/rno-let-7c
    hsa-miR-423- CLL
    5p/mmu-miR-423-5p
    hsa-miR-32* CLL
    hsa-miR-34b/mmu- CLL
    miR-34b-3p
    hsa-miR-551b/mmu- CLL
    miR-551b/rno-miR-
    551b
    hsa-let-7i/mmu-let- CLL
    7i/rno-let-7i
    hsa-miR-29a/mmu- CLL
    miR-29a/rno-miR-29a
    hsa-miR-138- CLL
    1*/mmu-miR-
    138*/rno-miR-138*
    hsa-miR-29b/mmu- CLL
    miR-29b/rno-miR-29b
    hsa-miR-191/mmu- CLL
    miR-191/rno-miR-191
    hsa-miR-26b/mmu- CLL
    miR-26b/rno-miR-26b
    hsa-miR-26a/mmu- CLL
    miR-26a/rno-miR-26a
    hsa-miR-550 CLL
    hsa-miR-374a CLL
    hsa-miR-142-5p/mmu- CLL
    miR-142-5p/rno-miR-
    142-5p
    hsa-miR-29c/mmu- CLL
    miR-29c/rno-miR-29c
    hsa-miR-140-3p/mmu- CLL
    miR-140*/rno-miR-
    140*
    hsa-miR-30e/mmu- CLL
    miR-30e/rno-miR-30e
    hsa-miR-801/mmu- CLL
    miR-801
    hsa-miR-768-3p CLL
    hsa-miR-549 CLL
    hsa-miR-199a-5p/mmu- CLL
    miR-199a-5p/rno-miR-
    199a-5p
    hsa-miR-223/mmu- CLL
    miR-223/rno-miR-223
    hsa-miR-101/mmu- CLL
    miR-101a/rno-miR-
    101a
    hsa-miR-888* CLL
    hsa-miR-24-1*/mmu- CLL
    miR-24-1*/rno-miR-24-
    1*
    hsa-miR-519d CLL
    hsa-miR-154/mmu- CLL
    miR-154/rno-miR-154
    hsa-miR-638 CLL
    hsa-miR-668/mmu- CLL
    miR-668
    hsa-miR-891a CLL
    hsa-miR-768-5p CLL
    hsa-miR-140-5p/mmu- CLL
    miR-140/rno-miR-140
    hsa-miR-196a*/mmu- CLL
    miR-196a*/rno-miR-
    196a*
    hsa-miR-150/mmu- CLL
    miR-150/rno-miR-150
    hsa-let-7g/mmu-let-7g CLL
    hsa-miR-363/mmu- CLL
    miR-363/rno-miR-363
    hsa-miR-486-5p/mmu- CLL
    miR-486
    hsa-miR-32/mmu-miR- CLL
    32/rno-miR-32
    hsa-miR-147 CLL
    hsa-miR-20b* CLL
    hsa-miR-487b/mmu- CLL
    miR-487b/rno-miR-
    487b
    hsa-miR-636 CLL
    hsa-miR-144* CLL
    hsa-miR-186/mmu- CLL
    miR-186/rno-miR-186
    hsa-miR-30e*/mmu- CLL
    miR-30e*/rno-miR-
    30e*
    hsa-miR-331-5p/mmu- CLL
    miR-331-5p
  • TABLE 23
    Predictor microRNAs that distinguish germinal center B-cell like
    (GCB) DLBCL from follicular lymphoma
    Higher
    GCB vs FL in
    hsa-miR-378/mmu- GCB
    miR-378/rno-miR-378
    hsa-miR-20b/mmu- GCB
    miR-20b/rno-miR-20b-
    5p
    hsa-miR-19b/mmu- GCB
    miR-19b/rno-miR-19b
    hsa-miR-106a GCB
    hsa-miR-17/mmu-miR- GCB
    17/rno-miR-17-5p/rno-
    miR-17
    hsa-miR-93/mmu-miR- GCB
    93/rno-miR-93
    hsa-miR-20a/mmu- GCB
    miR-20a/rno-miR-20a
    hsa-miR-23b/mmu- GCB
    miR-23b/rno-miR-23b
    hsa-miR-23a/mmu- GCB
    miR-23a/rno-miR-23a
    hsa-miR-22/mmu-miR- GCB
    22/rno-miR-22
    hsa-miR-19a/mmu- GCB
    miR-19a/rno-miR-19a
    hsa-miR-320/mmu- GCB
    miR-320/rno-miR-320
    hsa-miR-106b/mmu- GCB
    miR-106b/rno-miR-
    106b
    hsa-miR-103/mmu- GCB
    miR-103/rno-miR-103
    hsa-miR-30c/mmu- GCB
    miR-30c/rno-miR-30c
    ebv-miR-BHRF1-2 GCB
    hsa-miR-125a- GCB
    5p/mmu-miR-125a-
    5p/rno-miR-125a-5p
    hsa-let-7a/mmu-let- GCB
    7a/rno-let-7a
    hsa-miR-628-3p GCB
    hsa-let-7c/mmu-let- GCB
    7c/rno-let-7c
    hsa-miR-423-5p/mmu- FL
    miR-423-5p
    hsa-miR-24-1*/mmu- FL
    miR-24-1*/rno-miR-
    24-1*
    ebv-miR-BART2-3p FL
    hsa-miR-138-1*/mmu- FL
    miR-138*/rno-miR-
    138*
    hsa-miR-768-5p FL
    hsa-miR-30b* FL
    hsa-miR-494/mmu- FL
    miR-494/rno-miR-494
    hsa-miR-583 FL
    hsa-miR-185/mmu- FL
    miR-185/rno-miR-185
    hsa-miR-765 FL
    hsa-miR-34b/mmu- FL
    miR-34b-3p
    hsa-miR-921 FL
    hsa-miR-551b/mmu- FL
    miR-551b/rno-miR-
    551b
    hsa-miR-549 FL
    hsa-miR-939 FL
    hsa-miR-302d* FL
    ebv-miR-BART17-5p FL
    hsa-miR-801/mmu- FL
    miR-801
    hsa-miR-888* FL
    hsa-miR-620 FL
    hsa-miR-576-3p FL
    hsa-miR-32* FL
    hsa-miR-574-5p/mmu- FL
    miR-574-5p
    hsa-miR-505/rno-miR- FL
    505
    hsa-miR-885-5p FL
    hsa-miR-455-3p FL
    hsa-miR-152/mmu- FL
    miR-152/rno-miR-152
    hsa-miR-200b*/mmu- FL
    miR-200b*
    mghv-miR-M1-2 FL
    hcmv-miR-UL148D FL
    hsa-miR-497/mmu-miR- FL
    497/rno-miR-497
    ebv-miR-BART13 FL
    ebv-miR-BART16 FL
    hsa-miR-125b-2*/rno- FL
    miR-125b*
    hsa-miR-490-3p/mmu- FL
    miR-490
    hsa-miR-99b/mmu-miR- FL
    99b/rno-miR-99b
    hsa-miR-339-5p/mmu- FL
    miR-339-5p/rno-miR-
    339-5p
    hsa-miR-574-3p/mmu- FL
    miR-574-3p
    hsa-miR-515-5p FL
    hsa-miR-877/mmu-miR- FL
    877/rno-miR-877
    hsa-miR-208a/mmu-miR- FL
    208a/rno-miR-208
    hcmv-miR-US25-1* FL
    hsa-miR-326/mmu-miR- FL
    326/rno-miR-326
    hsa-miR-488 FL
    hsa-miR-629 FL
    hsa-miR-24-2*/mmu- FL
    miR-24-2*/rno-miR-24-
    2*
    hsa-miR-124/mmu-miR- FL
    124/rno-miR-124
    hsa-miR-493 FL
    hsv1-miR-H1 FL
    hsa-miR-484/mmu-miR- FL
    484/rno-miR-484
    hsa-miR-483-3p FL
    hsa-miR-27a*/mmu-miR- FL
    27a*/rno-miR-27a*
    hsa-miR-144* FL
    hsa-miR-617 FL
    hsa-miR-377* FL
    hsa-miR-363*/rno-miR- FL
    363*
    hsa-miR-148b/mmu-miR- FL
    148b/rno-miR-148b-3p
    kshv-miR-K12-1 FL
    hsa-miR-7/mmu-miR- FL
    7a/rno-miR-7a
    hsa-miR-193b* FL
    hsa-miR-542-3p/mmu- FL
    miR-542-3p/rno-miR-
    542-3p
    hsa-miR-601 FL
    hsa-miR-106b*/mmu- FL
    miR-106b*/rno-miR- FL
    106b*
    hsa-miR-7-2* FL
    kshv-miR-K12-6-5p FL
    hsa-miR-645 FL
    hsa-miR-524-5p FL
    hsa-miR-548d-5p FL
    hsa-miR-9*/mmu-miR- FL
    9*/rno-miR-9*
    hsa-miR-92a/mmu-miR- FL
    92a/rno-miR-92a
    hsa-miR-22*/mmu-miR- FL
    22*/rno-miR-22*
    hsa-miR-500* FL
    hsa-miR-890 FL
    hsa-miR-297/mmu-miR- FL
    297a
    hsa-miR-197/mmu-miR- FL
    197
    hsa-miR-20b* FL
    hsa-miR-629* FL
    hsa-miR-887 FL
    hsa-miR-425/mmu- FL
    miR-425/rno-miR-425
    hsa-miR-99b*/mmu- FL
    miR-99b*/rno-miR-
    99b*
    hsa-miR-513a-3p FL
    hsa-miR-206/mmu- FL
    miR-206/rno-miR-206
    hsa-miR-155* FL
    hsa-miR-181b/mmu- FL
    miR-181b/rno-miR-
    181b
    hsa-miR-299-3p FL
    hsa-miR-218-2*/mmu- FL
    miR-218-2*/rno-miR-
    218*
    mghv-miR-M1-8 FL
    ebv-miR-BART18-3p FL
    hsa-miR-708/mmu- FL
    miR-708/rno-miR-708
    hsa-miR-409-5p/mmu- FL
    miR-409-5p/rno-miR-
    409-5p
    hsa-miR-553 FL
    hsa-miR-361-3p FL
    hsa-miR-296-3p/mmu- FL
    miR-296-3p/rno-miR-
    296
    ebv-miR-BHRF1-3 FL
    hsa-miR-34c-5p/mmu- FL
    miR-34c/rno-miR-34c
    hsa-let-7b*/mmu-let- FL
    7b*/rno-let-7b*
    hsa-miR-301a/mmu- FL
    miR-301a/rno-miR-
    301a
    hsa-miR-122* FL
    hsa-miR-183/mmu- FL
    miR-183/rno-miR-183
    kshv-miR-K12-5 FL
    kshv-miR-K12-7 FL
    hsa-miR-552 FL
    hsa-miR-151-3p FL
    hsa-miR-194/mmu- FL
    miR-194/rno-miR-194
    hsa-miR-585 FL
    hsa-miR-340*/mmu- FL
    miR-340-3p/rno-miR-
    340-3p
    hsa-let-7d*/mmu-let- FL
    7d*/rno-let-7d*
    hsa-miR-622 FL
    hsa-miR-575 FL
    hsa-miR-514 FL
    hsa-miR-92b/mmu- FL
    miR-92b/rno-miR-92b
    hsa-miR-551a FL
    hsa-miR-221* FL
    hsa-miR-922 FL
    hsa-miR-938 FL
    hsa-miR-615-3p/mmu- FL
    miR-615-3p
    hsa-miR-220b FL
    hsa-miR-744/mmu- FL
    miR-744
    hsa-miR-657 FL
    hsa-miR-382/mmu- FL
    miR-382/rno-miR-382
    hsa-miR-518a-3p FL
    hsa-miR-138/mmu- FL
    miR-138/rno-miR-138
    hsa-miR-636 FL
    hsa-miR-96/mmu- FL
    miR-96/rno-miR-96
    hsa-miR-509-3-5p FL
    hsa-miR-337-3p FL
    hsa-miR-342-5p/mmu- FL
    miR-342-5p/rno-miR-
    342-5p
  • TABLE 24
    Predictor microRNAs that distinguish germinal center B-cell like
    (GCB) DLBCL from Hodgkin's lymphoma
    Higher
    GCB vs HL in
    hsa-miR-19b/mmu-miR- GCB
    19b/rno-miR-19b
    hsa-miR-19a/mmu-miR- GCB
    19a/rno-miR-19a
    hsa-miR-106a GCB
    hsa-miR-20b/mmu-miR- GCB
    20b/rno-miR-20b-5p
    hsa-miR-17/mmu-miR- GCB
    17/rno-miR-17-5p/rno-
    miR-17
    hsa-miR-15b/mmu-miR- GCB
    15b/rno-miR-15b
    hsa-miR-20a/mmu-miR- GCB
    20a/rno-miR-20a
    hsa-miR-30b/mmu-miR- GCB
    30b/rno-miR-30b-5p
    hsa-miR-142-3p/mmu-miR- GCB
    142-3p/rno-miR-142-3p
    hsa-miR-30c/mmu-miR- GCB
    30c/rno-miR-30c
    hsa-miR-378/mmu-miR- GCB
    378/rno-miR-378
    hsa-miR-93/mmu-miR- GCB
    93/rno-miR-93
    hsa-miR-106b/mmu-miR- GCB
    106b/rno-miR-106b
    hsa-miR-374a GCB
    hsa-miR-24/mmu-miR- GCB
    24/rno-miR-24
    hsa-miR-29b/mmu-miR- GCB
    29b/rno-miR-29b
    hsa-miR-22/mmu-miR- GCB
    22/rno-miR-22
    hsa-miR-142-5p/mmu-miR- GCB
    142-5p/rno-miR-142-5p
    hsa-miR-30e/mmu-miR- GCB
    30e/rno-miR-30e
    hsa-miR-30a/mmu-miR- GCB
    30a/rno-miR-30a
    hsa-miR-30d/mmu-miR- GCB
    30d/rno-miR-30d
    hsa-miR-23b/mmu-miR- GCB
    23b/rno-miR-23b
    hsa-miR-16/mmu-miR- GCB
    16/rno-miR-16
    hsa-miR-191/mmu-miR- GCB
    191/rno-miR-191
    hsa-miR-15a/mmu-miR- GCB
    15a
    hsa-miR-26b/mmu-miR- GCB
    26b/rno-miR-26b
    hsa-miR-23a/mmu-miR- GCB
    23a/rno-miR-23a
    hsa-let-7a/mmu-let-7a/rno- GCB
    let-7a
    hsa-miR-103/mmu-miR- GCB
    103/rno-miR-103
    hsa-miR-140-3p/mmu-miR- GCB
    140*/rno-miR-140*
    hsa-miR-154/mmu-miR- GCB
    154/rno-miR-154
    hsa-miR-320/mmu-miR- GCB
    320/rno-miR-320
    hsa-miR-550 GCB
    hsa-miR-125a-5p/mmu- GCB
    miR-125a-5p/rno-miR-
    125a-5p
    hsa-let-7c/mmu-let-7c/rno- GCB
    let-7c
    hsa-miR-185/mmu-miR- HL
    185/rno-miR-185
    hsa-miR-658 HL
    hsa-miR-549 HL
    hsa-miR-634 HL
    hsa-miR-551b/mmu-miR- HL
    551b/rno-miR-551b
    hsa-miR-518c* HL
    hsa-miR-888* HL
    hsa-miR-765 HL
    hsa-miR-423-5p/mmu-miR- HL
    423-5p
    hsa-miR-30c-2*/mmu-miR- HL
    30c-2*/rno-miR-30c-2*
    hsa-miR-503 HL
    hsa-miR-921 HL
    hsa-miR-520d-5p HL
    hsa-miR-574-5p/mmu-miR- HL
    574-5p
    hsa-miR-32* HL
    hsa-miR-939 HL
    ebv-miR-BART2-3p HL
    ebv-miR-BHRF1-2 HL
    hsa-miR-583 HL
    hsa-miR-30b* HL
    hsa-miR-149* HL
    mghv-miR-M1-4 HL
    hsa-miR-513a-5p HL
    hsa-miR-494/mmu-miR- HL
    494/rno-miR-494
    hsa-miR-498 HL
    hsa-miR-485-3p/mmu-miR- HL
    485*
    hsa-miR-129-5p/mmu-miR- HL
    129-5p/rno-miR-129
    hsa-miR-25* HL
    hsa-miR-923 HL
    hsa-miR-519d HL
    hsa-miR-516a-5p HL
    hsa-miR-99a/mmu-miR- HL
    99a/rno-miR-99a
    hsa-miR-943 HL
    hsa-miR-885-5p HL
    ebv-miR-BHRF1-1 HL
    hsa-miR-152/mmu-miR- HL
    152/rno-miR-152
    ebv-miR-BART8* HL
    hsa-miR-200b*/mmu-miR- HL
    200b*
    hsa-miR-125b-1*/mmu- HL
    miR-125b-3p/rno-miR-
    125b-3p
    hsa-miR-526b HL
    hsa-miR-29a*/mmu-miR- HL
    29a*/rno-miR-29a*
    hsa-miR-532-5p/mmu-miR- HL
    532-5p/rno-miR-532-5p
    hsa-miR-183*/mmu-miR- HL
    183*
    hsa-miR-659 HL
    hsa-miR-145*/mmu-miR- HL
    145*
    mghv-miR-M1-7-5p HL
    hsa-miR-143* HL
    hsa-miR-660 HL
    hsa-miR-130b/mmu- HL
    miR-130b/rno-miR-130b
    hsa-miR-671-5p/mmu- HL
    miR-671-5p
    hsa-miR-525-5p HL
    hsa-miR-505/rno-miR- HL
    505
    hsa-miR-488 HL
    hsa-miR-766 HL
    hsa-miR-20b* HL
    hsa-miR-339-5p/mmu- HL
    miR-339-5p/rno-miR-
    339-5p
    hsa-miR-524-5p HL
    hsa-miR-455-3p HL
    hsa-miR-92a/mmu-miR- HL
    92a/rno-miR-92a
    hsa-miR-502-3p HL
    hsa-miR-210/mmu-miR- HL
    210/rno-miR-210
    hsv1-miR-H1 HL
    ebv-miR-BART6-3p HL
    hsa-miR-490-3p/mmu- HL
    miR-490
    hsa-miR-149/mmu-miR- HL
    149
    hsa-miR-128/mmu-miR- HL
    128/rno-miR-128
    hsa-miR-635 HL
    hcmv-miR-UL148D HL
    hsa-miR-373* HL
    hsa-miR-647 HL
    hsa-miR-197/mmu-miR- HL
    197
    hsa-miR-602 HL
    hsa-miR-656 HL
    hsa-miR-874/mmu-miR- HL
    874/rno-miR-874
    ebv-miR-BART19-3p HL
    hsa-miR-551b* HL
    hsa-miR-96/mmu-miR- HL
    96/rno-miR-96
    hsa-miR-889 HL
    hsa-miR-425/mmu-miR- HL
    425/rno-miR-425
    hsa-miR-34c-5p/mmu- HL
    miR-34c/rno-miR-34c
    hcmv-miR-UL70-3p HL
    hsa-miR-27a*/mmu- HL
    miR-27a*/rno-miR-27a*
    hsa-miR-194/mmu-miR- HL
    194/rno-miR-194
    hsa-miR-17*/rno-miR- HL
    17-3p
    hsa-miR-548d-5p HL
    hsa-miR-7/mmu-miR- HL
    7a/rno-miR-7a
    hsa-miR-877/mmu-miR- HL
    877/rno-miR-877
    hsa-miR-22*/mmu-miR- HL
    22*/rno-miR-22*
    hsa-miR-323-3p/mmu- HL
    miR-323-3p/rno-miR-
    323
    hsa-miR-708/mmu-miR- HL
    708/rno-miR-708
    hsa-miR-513a-3p HL
    hsa-miR-595 HL
    hsa-miR-922 HL
    hsa-miR-515-5p HL
    hsa-miR-99b/mmu-miR- HL
    99b/rno-miR-99b
    hsa-miR-483-3p HL
    hsa-miR-330-5p/mmu- HL
    miR-330/rno-miR-330
    hsa-miR-509-3p HL
    hsa-miR-151-3p HL
    ebv-miR-BART13 HL
    hsa-miR-617 HL
    hsa-miR-328/mmu-miR- HL
    328/rno-miR-328
    hsa-miR-361-3p HL
    hsa-miR-138/mmu-miR- HL
    138/rno-miR-138
    ebv-miR-BART7* HL
    hsa-miR-589 HL
    hsa-miR-576-5p HL
    hsa-miR-452 HL
    hsa-miR-7-2* HL
    hsa-miR-296-5p/mmu- HL
    miR-296-5p/rno-miR-
    296*
    hsa-miR-550* HL
    hsa-miR-92b/mmu-miR- HL
    92b/rno-miR-92b
    kshv-miR-K12-1 HL
    hsa-miR-526a/hsa-miR- HL
    520c-5p/hsa-miR-518d-
    5p
    mghv-miR-M1-2 HL
    hsa-miR-548b-3p HL
    hsa-miR-297/mmu-miR- HL
    297a
    hsa-miR-195* HL
    hsa-miR-652/mmu-miR- HL
    652/rno-miR-652
    hsa-miR-221* HL
    hsa-miR-194* HL
    hsa-miR-23a*/rno-miR- HL
    23a*
    hsa-miR-125b-2*/rno- HL
    miR-125b*
    hsa-miR-212/mmu-miR- HL
    212/rno-miR-212
    ebv-miR-BART18-3p HL
    hsa-miR-586 HL
    hsa-miR-137/mmu-miR- HL
    137/rno-miR-137
    hsa-miR-610 HL
    hcmv-miR-UL112 HL
    hsa-miR-181b/mmu- HL
    miR-181b/rno-miR-181b
    hsa-miR-936 HL
    hsa-miR-744/mmu- HL
    miR-744
    kshv-miR-K12-6-5p HL
    hcmv-miR-US25-1* HL
    hsa-miR-21* HL
    mghv-miR-M1-6 HL
    mghv-miR-M1-8 HL
    hsa-miR-10a*/mmu- HL
    miR-10a*/rno-miR-
    10a-3p
    hsa-miR-345 HL
    hsa-miR-887 HL
    hsa-miR-193b* HL
    hsa-miR-122* HL
    kshv-miR-K12-5 HL
    hsa-miR-92b* HL
    hsa-miR-526b* HL
    hsa-miR-553 HL
    hsa-miR-601 HL
    hiv1-miR-H1 HL
    hsa-miR-623 HL
    hsa-miR-519e HL
    hsa-miR-650 HL
    hsa-miR-575 HL
    hsa-miR-629* HL
    hsa-miR-890 HL
    hsa-miR- HL
    150*/mmu-miR-
    150*
    hsa-miR- HL
    425*/mmu-miR-
    425*
    hsa-miR- HL
    135a*/mmu-miR-
    135a*
    hsa-miR-612 HL
    hsa-miR-636 HL
    hsa-miR-500 HL
    hsa-miR-502-5p HL
    hsa-miR-9*/mmu- HL
    miR-9*/rno-miR-9*
    hsa-miR-500* HL
    hsa-miR- HL
    124*/mmu-miR-
    124*/rno-miR-124*
    hsa-miR-30c- HL
    1*/mmu-miR-30c-
    1*/rno-miR-30c-1*
    hsa-miR- HL
    99b*/mmu-miR-
    99b*/rno-miR-99b*
    hsa-miR-331- HL
    5p/mmu-miR-331-
    5p
    hsa-miR-206/mmu- HL
    miR-206/rno-miR-
    206
    hsa-miR-376a* HL
    hsa-miR-585 HL
    hsa-miR-640 HL
    hsa-miR-377* HL
    hsa-miR-125a- HL
    3p/mmu-miR-125a-
    3p/rno-miR-125a-3p
    hsa-miR-24- HL
    2*/mmu-miR-24-
    2*/rno-miR-24-2*
    hsa-miR-484/mmu- HL
    miR-484/rno-miR-
    484
    hsa-miR- HL
    106b*/mmu-miR-
    106b*/rno-miR-
    106b*
    hsa-let-7b*/mmu- HL
    let-7b*/rno-let-7b*
    hsa-miR-302c* HL
    hsa-miR-542- HL
    5p/mmu-miR-542-
    5p/rno-miR-542-5p
    hsa-miR-622 HL
    ebv-miR-BHRF1-3 HL
    hsa-miR-181a-2* HL
    hsa-miR-183/mmu- HL
    miR-183/rno-miR-
    183
    hsa-miR-409- HL
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    ebv-miR-BART20- HL
    3p
    hsa-miR-629 HL
    hsa-let-7d*/mmu- HL
    let-7d*/rno-let-7d*
    hsa-miR-645 HL
    hsa-miR-492 HL
    hsa-miR-654-5p HL
    hsa-miR-208a/mmu- HL
    miR-208a/rno-miR-
    208
    hsa-miR-584 HL
    hsa-miR-382/mmu- HL
    miR-382/rno-miR-
    382
    hsa-miR- HL
    340*/mmu-miR-
    340-3p/rno-miR-
    340-3p
    hsa-miR-490-5p HL
    hsa-miR-663 HL
    hsa-miR-337-3p HL
    hsa-miR-518a-3p HL
    ebv-miR-BART9* HL
    hsa-miR-342- HL
    5p/mmu-miR-342-
    5p/rno-miR-342-5p
    hsa-miR-514 HL
    hsa-miR-508-5p HL
    hsa-miR-124/mmu- HL
    miR-124/rno-miR-
    124
    hsa-miR-657 HL
    hsa-miR-938 HL
    hsa-miR-296- HL
    3p/mmu-miR-296-
    3p/rno-miR-296
    hsa-miR-551a HL
    hsa-miR-542- HL
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    hsa-miR-220b HL
    hsa-miR-326/mmu- HL
    miR-326/rno-miR-
    326
    hsa-miR-615- HL
    3p/mmu-miR-615-
    3p
    hsa-miR-433/mmu- HL
    miR-433/rno-miR-
    433
    hsa-miR-202 HL
    hsa-miR-338- HL
    5p/mmu-miR-338-
    5p/rno-miR-338*
    hsa-miR-552 HL
    hsa-miR-299-3p HL
    hsa-miR-509-3-5p HL
  • TABLE 25
    Predictor microRNAs that distinguish Burkitt lymphoma
    from chromic lymphocytic leukemia
    Higher
    BL vs CLL in
    hsa-miR-874/mmu- BL
    miR-874/rno-miR-874
    hsa-miR-125b/mmu- BL
    miR-125b-5p/rno-miR-
    125b-5p
    hsa-miR-126/mmu- BL
    miR-126-3p/rno-miR-
    126
    ebv-miR-BHRF1-2 BL
    hsa-miR-193b BL
    hsa-miR-371-5p BL
    hsa-miR-193a-5p BL
    hsa-miR-628-3p BL
    hsa-miR-185* BL
    hsa-miR-503 BL
    hsa-miR-199a-3p/hsa- BL
    miR-199b-3p/mmu-
    miR-199a-3p/mmu-
    miR-199b/rno-miR-
    199a-3p
    hsa-miR-143/mmu- BL
    miR-143/rno-miR-143
    hsa-miR-130a/mmu- BL
    miR-130a/rno-miR-
    130a
    hsa-miR-145/mmu- BL
    miR-145/rno-miR-145
    hsa-miR-30b* BL
    hsa-miR-665 BL
    hsa-miR-658 BL
    hsa-miR-933 BL
    hsa-miR-30c-2*/mmu- BL
    miR-30c-2*/rno-miR-
    30c-2*
    hsa-miR-765 BL
    hsa-miR-620 BL
    hsa-miR-520d-5p BL
    hsa-miR-494/mmu- BL
    miR-494/rno-miR-494
    hsa-miR-551b/mmu- CLL
    miR-551b/rno-miR-
    551b
    hsa-miR-106b/mmu- CLL
    miR-106b/rno-miR-
    106b
    hsa-miR-30c/mmu- CLL
    miR-30c/rno-miR-30c
    hsa-miR-16/mmu-miR- CLL
    16/rno-miR-16
    hsa-miR-27a/mmu- CLL
    miR-27a/rno-miR-27a
    hsa-miR-27b/mmu- CLL
    miR-27b/rno-miR-27b
    hsa-miR-550 CLL
    hsa-miR-30a/mmu- CLL
    miR-30a/rno-miR-30a
    hsa-miR-30b/mmu-miR- CLL
    30b/rno-miR-30b-5p
    hsa-miR-34b/mmu-miR- CLL
    34b-3p
    hsa-miR-801/mmu-miR- CLL
    801
    hsa-miR-26b/mmu-miR- CLL
    26b/rno-miR-26b
    hsa-let-7b/mmu-let- CLL
    7b/rno-let-7b
    hsa-miR-142-5p/mmu- CLL
    miR-142-5p/rno-miR-
    142-5p
    hsa-miR-26a/mmu-miR- CLL
    26a/rno-miR-26a
    hsa-miR-29a/mmu-miR- CLL
    29a/rno-miR-29a
    hsa-miR-768-3p CLL
    hsa-miR-199a-5p/mmu- CLL
    miR-199a-5p/rno-miR-
    199a-5p
    hsa-miR-30e/mmu-miR- CLL
    30e/rno-miR-30e
    hsa-miR-29b/mmu-miR- CLL
    29b/rno-miR-29b
    hsa-miR-101/mmu-miR- CLL
    101a/rno-miR-101a
    hsa-miR-138-1*/mmu- CLL
    miR-138*/rno-miR-138*
    hsa-miR-195/mmu-miR- CLL
    195/rno-miR-195
    hsa-miR-549 CLL
    hsa-miR-103/mmu-miR- CLL
    103/rno-miR-103
    hsa-miR-649 CLL
    hsa-miR-335/mmu-miR- CLL
    335-5p/rno-miR-335
    hsa-miR-342-3p/mmu- CLL
    miR-342-3p/rno-miR-
    342-3p
    hsa-miR-423-3p/mmu- CLL
    miR-423-3p/rno-miR-
    423
    hsa-miR-222/mmu-miR- CLL
    222/rno-miR-222
    hsa-miR-374a CLL
    hsa-miR-888* CLL
    hsa-miR-30d/mmu-miR- CLL
    30d/rno-miR-30d
    hsa-miR-299-5p/mmu- CLL
    miR-299*/rno-miR-299
    hsa-miR-107/mmu-miR- CLL
    107/rno-miR-107
    hsa-miR-105 CLL
    hsa-let-7f/mmu-let- CLL
    7f/rno-let-7f
    hsa-miR-191/mmu-miR- CLL
    191/rno-miR-191
    hsa-miR-223/mmu-miR- CLL
    223/rno-miR-223
    hsa-miR-361-5p/mmu- CLL
    miR-361/rno-miR-361
    hsa-miR-29c/mmu- CLL
    miR-29c/rno-miR-29c
    hsa-miR-147 CLL
    hsa-miR-361-3p CLL
    hsa-miR-140-3p/mmu- CLL
    miR-140*/rno-miR-
    140*
    hsa-miR-486-5p/mmu- CLL
    miR-486
    hsa-miR-33a/mmu- CLL
    miR-33/rno-miR-33
    hsa-miR-636 CLL
    hsa-miR-24-1*/mmu- CLL
    miR-24-1*/rno-miR-24-
    1*
    hsa-miR-144* CLL
    hsa-miR-668/mmu- CLL
    miR-668
    hsa-miR-768-5p CLL
    hsa-miR-363/mmu- CLL
    miR-363/rno-miR-363
    hsa-miR-150/mmu- CLL
    miR-150/rno-miR-150
    hsa-miR-519d CLL
    hsa-miR-891a CLL
    hsa-miR-186/mmu- CLL
    miR-186/rno-miR-186
    hsa-miR-331-5p/mmu- CLL
    miR-331-5p
    hsa-miR-28-5p/mmu- CLL
    miR-28/rno-miR-28
    hsa-miR-154/mmu- CLL
    miR-154/rno-miR-154
    hsa-miR-155 CLL
    hsa-miR-363*/rno-miR- CLL
    363*
    hsa-miR-32/mmu-miR- CLL
    32/rno-miR-32
    hsa-miR-30e*/mmu- CLL
    miR-30e*/rno-miR-
    30e*
    hsa-miR-140-5p/mmu- CLL
    miR-140/rno-miR-140
    hsa-let-7g/mmu-let-7g CLL
    hsa-miR-20b* CLL
    hsa-miR-129* CLL
    hsa-miR-196a*/mmu- CLL
    miR-196a*/rno-miR-
    196a*
    hsa-miR-487b/mmu- CLL
    miR-487b/rno-miR-
    487b
  • TABLE 26
    Predictor microRNAs that distinguish Burkitt lymphoma
    from follicular lymphoma
    Higher
    BL vs FL in
    hsa-miR-17/mmu-miR- BL
    17/rno-miR-17-5p/rno-
    miR-17
    hsa-miR-106a BL
    hsa-miR-19b/mmu-miR- BL
    19b/rno-miR-19b
    hsa-miR-20a/mmu-miR- BL
    20a/rno-miR-20a
    hsa-miR-19a/mmu-miR- BL
    19a/rno-miR-19a
    hsa-miR-628-3p BL
    hsa-miR-503 BL
    hsa-miR-371-5p BL
    hsa-miR-106b/mmu- BL
    miR-106b/rno-miR-106b
    hsa-miR-30c-2*/mmu- BL
    miR-30c-2*/rno-miR-
    30c-2*
    ebv-miR-BART2-3p FL
    hsa-let-7e/mmu-let- FL
    7e/rno-let-7e
    hsa-miR-551b/mmu- FL
    miR-551b/rno-miR-551b
    hsa-miR-26b/mmu-miR- FL
    26b/rno-miR-26b
    hsa-miR-26a/mmu-miR- FL
    26a/rno-miR-26a
    hsa-miR-620 FL
    hsa-miR-801/mmu-miR- FL
    801
    ebv-miR-BART17-5p FL
    hsa-miR-29a/mmu-miR- FL
    29a/rno-miR-29a
    hsa-miR-34b/mmu-miR- FL
    34b-3p
    hsa-miR-32* FL
    hsa-miR-29b/mmu-miR- FL
    29b/rno-miR-29b
    hsa-miR-649 FL
    hsa-miR-576-3p FL
    hsa-miR-302a/mmu- FL
    miR-302a
    hsa-miR-365/mmu-miR- FL
    365/rno-miR-365
    hsa-miR-148a/mmu- FL
    miR-148a
    hsa-miR-146b-5p/mmu- FL
    miR-146b/rno-miR-146b
    hsa-miR-505/rno-miR- FL
    505
    hsa-miR-33a/mmu-miR- FL
    33/rno-miR-33
    hsa-miR-455-3p FL
    hsa-miR-374b/mmu- FL
    miR-374/rno-miR-374
    hsa-miR-214/mmu-miR- FL
    214/rno-miR-214
    hsa-miR-138-1*/mmu- FL
    miR-138*/rno-miR-138*
    hsa-miR-140-3p/mmu- FL
    miR-140*/rno-miR-140*
    hsa-miR-212/mmu-miR- FL
    212/rno-miR-212
    hsa-miR-29c/mmu-miR- FL
    29c/rno-miR-29c
    hsa-miR-888* FL
    hsa-miR-222/mmu-miR- FL
    222/rno-miR-222
    hsa-miR-152/mmu-miR- FL
    152/rno-miR-152
    hsa-miR-183*/mmu- FL
    miR-183*
    hsa-miR-768-5p FL
    hsa-miR-107/mmu-miR- FL
    107/rno-miR-107
    hsa-miR-574-5p/mmu- FL
    miR-574-5p
    hsa-miR-154/mmu-miR- FL
    154/rno-miR-154
    hsa-miR-620 FL
    hsa-miR-886-5p FL
    hsa-miR-208a/mmu- FL
    miR-208a/rno-miR-208
    hsa-miR-374b* FL
    hsa-miR-525-5p FL
    hsa-miR-363/mmu-miR- FL
    363/rno-miR-363
    hsa-miR-99b/mmu-miR- FL
    99b/rno-miR-99b
    hsa-miR-148b/mmu- FL
    miR-148b/rno-miR-
    148b-3p
    kshv-miR-K12-6-5p FL
    hsa-miR-125b-1*/mmu- FL
    miR-125b-3p/rno-miR-
    125b-3p
    hsa-miR-526b FL
    hsa-miR-629 FL
    hsa-miR-617 FL
    hsa-miR-124/mmu-miR- FL
    124/rno-miR-124
    hsa-miR-493 FL
    hsa-miR-24-1*/mmu- FL
    miR-24-1*/rno-miR-
    24-1*
    hsa-miR-200b*/mmu- FL
    miR-200b*
    hsa-miR-484/mmu- FL
    miR-484/rno-miR-484
    hsa-miR-483-3p FL
    hsa-miR-516b FL
    hsa-miR-125b-2*/rno- FL
    miR-125b*
    hsa-miR-490-3p/mmu- FL
    miR-490
    hsa-miR-140-5p/mmu- FL
    miR-140/rno-miR-140
    hsa-miR-877/mmu- FL
    miR-877/rno-miR-877
    hsa-miR-381/mmu- FL
    miR-381/rno-miR-381
    hsa-miR-193b* FL
    hsa-miR-635 FL
    hsa-miR-542-3p/mmu- FL
    miR-542-3p/rno-miR-
    542-3p
    hsa-miR-181a-2* FL
    hsa-miR-32/mmu- FL
    miR-32/rno-miR-32
    hsa-miR-105 FL
    hsa-miR-488 FL
    hsa-miR-505* FL
    ebv-miR-BART16 FL
    hsa-miR-891a FL
    hsa-miR-221/mmu- FL
    miR-221/rno-miR-221
    hsa-miR-7/mmu-miR- FL
    7a/rno-miR-7a
    hsa-miR-299-3p FL
    hsa-miR-575 FL
    hsa-miR-585 FL
    hsa-miR-30e*/mmu- FL
    miR-30e*/rno-miR-
    30e*
    hcmv-miR-US25-1* FL
    hsa-miR-708/mmu- FL
    miR-708/rno-miR-708
    hsv1-miR-H1 FL
    hsa-let-7g/mmu-let-7g FL
    hsa-miR-146a/mmu- FL
    miR-146a/rno-miR-
    146a
    ebv-miR-BART8* FL
    hsa-miR-106b*/mmu- FL
    miR-106b*/rno-miR-
    106b*
    hsa-miR-601 FL
    hsa-miR-553 FL
    hsa-miR-518b FL
    hsa-miR-548d-5p FL
    hsa-miR-382/mmu- FL
    miR-382/rno-miR-382
    hsa-miR-630 FL
    hsa-miR-144* FL
    hsa-miR-519d FL
    mghv-miR-M1-3 FL
    hsa-miR-497/mmu- FL
    miR-497/rno-miR-497
    hsa-miR-524-5p FL
    hsa-miR-500* FL
    hsa-miR-920 FL
    hsa-miR-297/mmu- FL
    miR-297a
    hsa-miR-509-3-5p FL
    hsa-miR-340*/mmu- FL
    miR-340-3p/rno-miR-
    340-3p
    hsa-miR-99b*/mmu- FL
    miR-99b*/rno-miR-
    99b*
    hsa-miR-887 FL
    hsa-miR-331-3p/mmu- FL
    miR-331-3p/rno-miR-
    331
    hsa-miR-206/mmu- FL
    miR-206/rno-miR-206
    hsa-miR-377* FL
    mghv-miR-M1-8 FL
    hsa-miR-513a-3p FL
    hsa-miR-146b-3p FL
    hsa-miR-155* FL
    hsa-miR-574-3p/mmu- FL
    miR-574-3p
    hsa-miR-615-3p/mmu- FL
    miR-615-3p
    hsa-miR-28-5p/mmu- FL
    miR-28/rno-miR-28
    hsa-miR-934 FL
    hsa-miR-151-5p/mmu- FL
    miR-151-5p/rno-miR-
    151
    hsa-miR-885-5p FL
    hsa-miR-409-5p/mmu- FL
    miR-409-5p/rno-miR-
    409-5p
    hsa-let-7d*/mmu-let- FL
    7d*/rno-let-7d*
    hsa-miR-155 FL
    hsa-let-7b*/mmu-let- FL
    7b*/rno-let-7b*
    hsa-miR-7-2* FL
    hsa-miR-221* FL
    hsa-miR-9*/mmu-miR- FL
    9*/rno-miR-9*
    hsa-miR-122* FL
    hsa-miR-130b/mmu- FL
    miR-130b/rno-miR-
    130b
    hsa-miR-183/mmu- FL
    miR-183/rno-miR-183
    hsa-miR-92a/mmu- FL
    miR-92a/rno-miR-92a
    hsa-miR-890 FL
    hsa-miR-938 FL
    kshv-miR-K12-7 FL
    hsa-miR-629* FL
    hsa-miR-922 FL
    kshv-miR-K12-5 FL
    hsa-miR-197/mmu- FL
    miR-197
    hsa-miR-552 FL
    hsa-miR-151-3p FL
    hsa-miR-194/mmu- FL
    miR-194/rno-miR-194
    hsa-miR-218-2*/mmu- FL
    miR-218-2*/rno-miR-
    218*
    hsa-miR-181b/mmu- FL
    miR-181b/rno-miR-
    181b
    ebv-miR-BART18-3p FL
    hsa-miR-34c-5p/mmu- FL
    miR-34c/rno-miR-34c
    hsa-miR-622 FL
    hsa-miR-514 FL
    hsa-miR-657 FL
    hsa-miR-518a-3p FL
    hsa-miR-647 FL
    hsa-miR-22*/mmu- FL
    miR-22*/rno-miR-22*
    hsa-miR-196a*/mmu- FL
    miR-196a*/rno-miR-
    196a*
    kshv-miR-K12-1 FL
    hsa-miR-425/mmu- FL
    miR-425/rno-miR-425
    hsa-miR-361-3p FL
    hsa-miR-220b FL
    hsa-miR-744/mmu- FL
    miR-744
    hsa-miR-551a FL
    hsa-miR-301a/mmu- FL
    miR-301a/rno-miR-
    301a
    hsa-miR-92b/mmu- FL
    miR-92b/rno-miR-92b
    hsa-miR-487b/mmu- FL
    miR-487b/rno-miR-
    487b
    hsa-miR-363*/rno-miR- FL
    363*
    hsa-miR-337-3p FL
    hsa-miR-636 FL
    hsa-miR-600 FL
    hsa-miR-138/mmu- FL
    miR-138/rno-miR-138
    hsa-miR-96/mmu-miR- FL
    96/rno-miR-96
    hsa-miR-20b* FL
    hsa-miR-342-5p/mmu- FL
    miR-342-5p/rno-miR-
    342-5p
    hsa-miR-215 FL
    hsa-miR-129* FL
  • TABLE 27
    Predictor microRNAs that distinguish Burkitt lymphoma
    from Hodgkin's lymphoma
    Higher
    BL vs HL in
    hsa-miR-19b/mmu-miR- BL
    19b/rno-miR-19b
    hsa-miR-19a/mmu-miR- BL
    19a/rno-miR-19a
    hsa-miR-17/mmu-miR- BL
    17/rno-miR-17-5p/rno-
    miR-17
    hsa-miR-106a BL
    hsa-miR-20a/mmu-miR- BL
    20a/rno-miR-20a
    hsa-miR-106b/mmu-miR- BL
    106b/rno-miR-106b
    hsa-miR-30c/mmu-miR- BL
    30c/rno-miR-30c
    hsa-miR-551b/mmu-miR- HL
    551b/rno-miR-551b
    hsa-miR-921 HL
    ebv-miR-BART2-3p HL
    hsa-miR-32* HL
    hsa-miR-494/mmu-miR- HL
    494/rno-miR-494
    hsa-miR-29c/mmu-miR- HL
    29c/rno-miR-29c
    hsa-miR-923 HL
    hsa-miR-199b-5p HL
    hsa-miR-148a/mmu-miR- HL
    148a
    hsa-miR-130a/mmu-miR- HL
    130a/rno-miR-130a
    hsa-miR-154/mmu-miR- HL
    154/rno-miR-154
    hsa-miR-151-5p/mmu- HL
    miR-151-5p/rno-miR-151
    hsa-miR-28-5p/mmu- HL
    miR-28/rno-miR-28
    hsa-miR-365/mmu-miR- HL
    365/rno-miR-365
    hsa-miR-602 HL
    hsa-miR-222/mmu-miR- HL
    222/rno-miR-222
    hsa-miR-214/mmu-miR- HL
    214/rno-miR-214
    hsa-miR-144* HL
    hsa-miR-107/mmu-miR- HL
    107/rno-miR-107
    hsa-miR-497/mmu-miR- HL
    497/rno-miR-497
    hsa-let-7g/mmu-let-7g HL
    hsa-miR-146a/mmu-miR- HL
    146a/rno-miR-146a
    hsa-miR-186/mmu-miR- HL
    186/rno-miR-186
    hsa-miR-886-5p HL
    hsa-miR-152/mmu-miR- HL
    152/rno-miR-152
    hsa-miR-29a*/mmu-miR- HL
    29a*/rno-miR-29a*
    hsa-miR-140-5p/mmu- HL
    miR-140/rno-miR-140
    hsa-miR-532-5p/mmu- HL
    miR-532-5p/rno-miR-
    532-5p
    hsa-miR-145*/mmu-miR- HL
    145*
    hsa-miR-515-5p HL
    hsa-miR-153/mmu-miR- HL
    153/rno-miR-153
    hsa-miR-513a-5p HL
    hsa-miR-516a-5p HL
    hsa-miR-660 HL
    hsa-miR-29c*/mmu-miR- HL
    29c*/rno-miR-29c*
    hsa-miR-505/rno-miR- HL
    505
    hsa-miR-455-3p HL
    hsa-miR-519e* HL
    hsa-miR-502-3p HL
    hsa-miR-922 HL
    hsa-miR-524-5p HL
    hsa-miR-483-5p HL
    hsa-miR-708/mmu-miR- HL
    708/rno-miR-708
    hsa-miR-498 HL
    ebv-miR-BART19-3p HL
    hsa-miR-149/mmu-miR- HL
    149
    hsa-miR-574-3p/mmu- HL
    miR-574-3p
    hsa-miR-659 HL
    hsa-miR-331-3p/mmu- HL
    miR-331-3p/rno-miR-331
    hsa-miR-105 HL
    hsa-miR-128/mmu-miR- HL
    128/rno-miR-128
    hsa-miR-200b*/mmu- HL
    miR-200b*
    hsa-miR-381/mmu-miR- HL
    381/rno-miR-381
    hsa-miR-766 HL
    hsa-miR-557 HL
    ebv-miR-BART16 HL
    hsa-miR-488 HL
    hsa-miR-516b HL
    mghv-miR-M1-2 HL
    hsa-miR-891a HL
    hsa-miR-221/mmu-miR- HL
    221/rno-miR-221
    hsa-miR-146b-3p HL
    hsa-miR-526b HL
    mghv-miR-M1-3 HL
    hsa-miR-505* HL
    hsv1-miR-H1 HL
    hcmv-miR-UL70-3p HL
    hsa-miR-24-2*/mmu- HL
    miR-24-2*/rno-miR-24-
    2*
    hsa-miR-617 HL
    hsa-miR-194/mmu-miR- HL
    194/rno-miR-194
    hsa-miR-934 HL
    hsa-miR-220c HL
    hsa-miR-548d-5p HL
    hsa-miR-937 HL
    ebv-miR-BART13 HL
    hsa-miR-7/mmu-miR- HL
    7a/rno-miR-7a
    hsa-miR-210/mmu-miR- HL
    210/rno-miR-210
    hsa-miR-490-3p/mmu- HL
    miR-490
    hsa-miR-221* HL
    hsa-miR-92a/mmu-miR- HL
    92a/rno-miR-92a
    hsa-miR-183*/mmu-miR- HL
    183*
    hsa-miR-513a-3p HL
    hsa-miR-575 HL
    hsa-miR-595 HL
    hsa-miR-920 HL
    hsa-miR-483-3p HL
    hsa-miR-330-5p/mmu- HL
    miR-330/rno-miR-330
    hsa-miR-525-5p HL
    hsa-miR-99b/mmu-miR- HL
    99b/rno-miR-99b
    hsa-miR-509-3p HL
    hsa-miR-151-3p HL
    ebv-miR-BHRF1-1 HL
    hsa-miR-630 HL
    mghv-miR-M1-7-3p HL
    hsa-miR-328/mmu-miR- HL
    328/rno-miR-328
    hsa-miR-452 HL
    hsa-miR-635 HL
    ebv-miR-BART5 HL
    hsa-miR-373* HL
    hsa-miR-96/mmu-miR- HL
    96/rno-miR-96
    hsa-miR-382/mmu-miR- HL
    382/rno-miR-382
    hsa-miR-155 HL
    hsa-miR-197/mmu-miR- HL
    197
    kshv-miR-K12-6-5p HL
    hcmv-miR-UL112 HL
    hsa-miR-551b* HL
    hsa-miR-877/mmu-miR- HL
    877/rno-miR-877
    hsa-miR-589 HL
    hsa-miR-936 HL
    hsa-miR-34c-5p/mmu- HL
    miR-34c/rno-miR-34c
    hsa-miR-885-5p HL
    ebv-miR-BART6-3p HL
    hsa-miR-585 HL
    hsa-miR-302c* HL
    hsa-miR-196a*/mmu- HL
    miR-196a*/rno-miR-
    196a*
    hsa-miR-195* HL
    hsa-miR-17*/rno-miR-17- HL
    3p
    hsa-miR-296-5p/mmu- HL
    miR-296-5p/rno-miR-
    296*
    hsa-miR-550* HL
    ebv-miR-BHRF1-3 HL
    hsa-miR-296-3p/mmu- HL
    miR-296-3p/rno-miR-296
    hsa-miR-526b* HL
    hsa-miR-548b-3p HL
    hsa-miR-652/mmu-miR- HL
    652/rno-miR-652
    hsa-miR-297/mmu-miR- HL
    297a
    hsa-miR-553 HL
    hsa-miR-194* HL
    hsa-miR-23a*/rno-miR- HL
    23a*
    hsa-miR-130b/mmu-miR- HL
    130b/rno-miR-130b
    hsa-miR-586 HL
    hsa-miR-137/mmu-miR- HL
    137/rno-miR-137
    hsa-miR-610 HL
    mghv-miR-M1-8 HL
    hsa-miR-193b* HL
    hsa-miR-519d HL
    hsa-miR-125b-1*/mmu- HL
    miR-125b-3p/rno-miR-
    125b-3p
    hsa-miR-744/mmu-miR- HL
    744
    hsa-miR-138/mmu-miR- HL
    138/rno-miR-138
    hsa-miR-21* HL
    hsa-miR-576-5p HL
    hsa-miR-125a-3p/mmu- HL
    miR-125a-3p/rno-miR-
    125a-3p
    mghv-miR-M1-6 HL
    hsa-miR-425/mmu-miR- HL
    425/rno-miR-425
    hsa-miR-10a*/mmu-miR- HL
    10a*/rno-miR-10a-3p
    hsa-miR-215 HL
    hsa-miR-345 HL
    hsa-miR-887 HL
    hsa-miR-7-2* HL
    hsa-miR-122* HL
    hsa-miR-363*/rno-miR- HL
    363*
    hsa-miR-22*/mmu-miR- HL
    22*/rno-miR-22*
    hsa-miR-542-5p/mmu- HL
    miR-542-5p/rno-miR-
    542-5p
    hsa-miR-92b* HL
    hsa-miR-526a/hsa- HL
    miR-520c-5p/hsa-
    miR-518d-5p
    kshv-miR-K12-5 HL
    hsa-miR- HL
    340*/mmu-miR-
    340-3p/rno-miR-
    340-3p
    hsa-let-7d*/mmu- HL
    let-7d*/rno-let-7d*
    hsa-miR-92b/mmu- HL
    miR-92b/rno-miR-
    92b
    hsa-miR-518b HL
    hiv1-miR-H1 HL
    hsa-miR-623 HL
    hsa-miR-645 HL
    hsa-miR-601 HL
    hsa-miR-519e HL
    hsa-miR-650 HL
    hsa-miR-361-3p HL
    hsa-miR- HL
    150*/mmu-miR-
    150*
    hsa-miR- HL
    425*/mmu-miR-
    425*
    hsa-miR- HL
    135a*/mmu-miR-
    135a*
    hsa-miR-518a-3p HL
    hsa-miR-612 HL
    hsa-miR-212/mmu- HL
    miR-212/rno-miR-
    212
    hsa-miR-125b- HL
    2*/rno-miR-125b*
    hsa-miR-500 HL
    hsa-miR-663 HL
    hsa-miR-647 HL
    hsa-miR-502-5p HL
    ebv-miR-BART18- HL
    3p
    hsa-miR- HL
    99b*/mmu-miR-
    99b*/rno-miR-99b*
    ebv-miR-BART7* HL
    hsa-miR-500* HL
    hsa-miR- HL
    124*/mmu-miR-
    124*/rno-miR-124*
    hsa-miR-206/mmu- HL
    miR-206/rno-miR-
    206
    hsa-miR-615- HL
    3p/mmu-miR-615-
    3p
    hsa-miR-30c- HL
    1*/mmu-miR-30c-
    1*/rno-miR-30c-1*
    hsa-miR-331- HL
    5p/mmu-miR-331-
    5p
    hcmv-miR-US25-1* HL
    hsa-miR-326/mmu- HL
    miR-326/rno-miR-
    326
    hsa-miR- HL
    181b/mmu-miR-
    181b/rno-miR-181b
    hsa-miR-376a* HL
    hsa-miR-433/mmu- HL
    miR-433/rno-miR-
    433
    hsa-miR-640 HL
    hsa-miR-938 HL
    hsa-miR-508-5p HL
    hsa-miR-484/mmu- HL
    miR-484/rno-miR-
    484
    hsa-miR- HL
    106b*/mmu-miR-
    106b*/rno-miR-
    106b*
    hsa-miR-600 HL
    hsa-let-7b*/mmu- HL
    let-7b*/rno-let-7b*
    hsa-miR-20b* HL
    hsa-miR-622 HL
    hsa-miR-657 HL
    hsa-miR-183/mmu- HL
    miR-183/rno-miR-
    183
    hsa-miR-409- HL
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    ebv-miR-BART20- HL
    3p
    ebv-miR-BART8* HL
    hsa-miR-129* HL
    hsa-miR-629 HL
    hsa-miR-890 HL
    hsa-miR-208a/mmu- HL
    miR-208a/rno-miR-
    208
    hsa-miR-492 HL
    hsa-miR-629* HL
    hsa-miR-654-5p HL
    hsa-miR-584 HL
    hsa-miR-636 HL
    hsa-miR-490-5p HL
    hsa-miR-337-3p HL
    hsa-miR-9*/mmu- HL
    miR-9*/rno-miR-9*
    ebv-miR-BART9* HL
    hsa-miR-509-3-5p HL
    hsa-miR-342- HL
    5p/mmu-miR-342-
    5p/rno-miR-342-5p
    hsa-miR-514 HL
    hsa-miR-377* HL
    kshv-miR-K12-1 HL
    hsa-miR-124/mmu- HL
    miR-124/rno-miR-
    124
    hsa-miR-542- HL
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    hsa-miR-220b HL
    hsa-miR-299-3p HL
    hsa-miR-181a-2* HL
    hsa-miR-202 HL
    hsa-miR- HL
    487b/mmu-miR-
    487b/rno-miR-487b
    hsa-miR-551a HL
    hsa-miR-338- HL
    5p/mmu-miR-338-
    5p/rno-miR-338*
    hsa-miR-552 HL
  • TABLE 28
    Predictor microRNAs that distinguish chronic lymphocytic leukemia
    from follicular lymphoma
    Higher
    CLL vs FL in
    hsa-miR-331-5p/mmu- CLL
    miR-331-5p
    hsa-miR-144/mmu-miR- CLL
    144/rno-miR-144
    hsa-miR-150/mmu-miR- CLL
    150/rno-miR-150
    hsa-miR-140-5p/mmu- CLL
    miR-140/rno-miR-140
    hsa-miR-335/mmu-miR- CLL
    335-5p/rno-miR-335
    hsa-miR-186/mmu-miR- CLL
    186/rno-miR-186
    hsa-miR-486-5p/mmu- CLL
    miR-486
    hsa-miR-154/mmu-miR- CLL
    154/rno-miR-154
    hsa-miR-223/mmu-miR- CLL
    223/rno-miR-223
    hsa-miR-299-5p/mmu- CLL
    miR-299*/rno-miR-299
    hsa-let-7g/mmu-let-7g CLL
    hsa-miR-32/mmu-miR- CLL
    32/rno-miR-32
    hsa-miR-30e*/mmu-miR- CLL
    30e*/rno-miR-30e*
    hsa-miR-147 CLL
    hsa-miR-20b/mmu-miR- CLL
    20b/rno-miR-20b-5p
    hsa-miR-101/mmu-miR- CLL
    101a/rno-miR-101a
    hsa-let-7f/mmu-let-7f/rno- CLL
    let-7f
    hsa-miR-30e/mmu-miR- CLL
    30e/rno-miR-30e
    hsa-miR-668/mmu-miR- CLL
    668
    hsa-miR-768-5p CLL
    hsa-miR-19a/mmu-miR- CLL
    19a/rno-miR-19a
    hsa-miR-199a-5p/mmu- CLL
    miR-199a-5p/rno-miR-
    199a-5p
    hsa-miR-638 CLL
    hsa-miR-196a*/mmu-miR- CLL
    196a*/rno-miR-196a*
    hsa-miR-19b/mmu-miR- CLL
    19b/rno-miR-19b
    hsa-miR-30d/mmu-miR- CLL
    30d/rno-miR-30d
    hsa-miR-363/mmu-miR- CLL
    363/rno-miR-363
    hsa-miR-374a CLL
    hsa-miR-140-3p/mmu- CLL
    miR-140*/rno-miR-140*
    hsa-miR-185/mmu-miR- CLL
    185/rno-miR-185
    hsa-miR-106b/mmu-miR- CLL
    106b/rno-miR-106b
    hsa-miR-106a CLL
    hsa-miR-191/mmu-miR- CLL
    191/rno-miR-191
    hsa-miR-17/mmu-miR- CLL
    17/rno-miR-17-5p/rno-
    miR-17
    hsa-let-7i/mmu-let-7i/rno- CLL
    let-7i
    hsa-miR-20a/mmu-miR- CLL
    20a/rno-miR-20a
    hsa-miR-142-5p/mmu- CLL
    miR-142-5p/rno-miR-142-
    5p
    hsa-miR-768-3p CLL
    hsa-miR-30b/mmu-miR- CLL
    30b/rno-miR-30b-5p
    hsa-miR-891a CLL
    hsa-miR-24-1*/mmu-miR- CLL
    24-1*/rno-miR-24-1*
    hsa-miR-29c/mmu-miR- CLL
    29c/rno-miR-29c
    hsa-miR-28-5p/mmu-miR- CLL
    28/rno-miR-28
    hsa-miR-30a/mmu-miR- CLL
    30a/rno-miR-30a
    hsa-miR-155 CLL
    hsa-miR-361-5p/mmu- CLL
    miR-361/rno-miR-361
    hsa-miR-15a/mmu-miR- CLL
    15a
    hsa-miR-26a/mmu-miR- CLL
    26a/rno-miR-26a
    hsa-miR-30c/mmu-miR- CLL
    30c/rno-miR-30c
    hsa-miR-541* CLL
    hsa-miR-26b/mmu-miR- CLL
    26b/rno-miR-26b
    hsa-miR-519d CLL
    hsa-miR-15b/mmu-miR- CLL
    15b/rno-miR-15b
    hsa-miR-550 CLL
    hsa-miR-29b/mmu-miR- CLL
    29b/rno-miR-29b
    hsa-miR-29a/mmu-miR- CLL
    29a/rno-miR-29a
    hsa-miR-103/mmu-miR- CLL
    103/rno-miR-103
    hsa-miR-423-3p/mmu- CLL
    miR-423-3p/rno-miR-423
    hsa-miR-549 CLL
    hsa-miR-107/mmu-miR- CLL
    107/rno-miR-107
    hsa-miR-888* CLL
    hsa-miR-801/mmu-miR- CLL
    801
    hsa-miR-149* FL
    hsa-miR-634 FL
    ebv-miR-BART2-3p FL
    hsa-miR-921 FL
    hsa-miR-494/mmu-miR- FL
    494/rno-miR-494
    hsa-miR-933 FL
    mghv-miR-M1-4 FL
    hsa-let-7e/mmu-let-7e/rno- FL
    let-7e
    hsa-miR-939 FL
    hsa-miR-518c* FL
    hsa-miR-32* FL
    hsa-miR-491-3p FL
    hsa-miR-185/mmu-miR- FL
    185/rno-miR-185
    hsa-miR-765 FL
    ebv-miR-BART17-5p FL
    hsa-miR-576-3p FL
    hsa-miR-658 FL
    hsa-miR-503 FL
    hsa-miR-30b* FL
    hsa-miR-302a/mmu-miR- FL
    302a
    hsa-miR-628-3p FL
    hsa-miR-642 FL
    hsa-miR-620 FL
    hsa-miR-99a/mmu- FL
    miR-99a/rno-miR-
    99a
    hsa-miR-371-5p FL
    hsa-miR-452 FL
    hsa-miR-126*/mmu- FL
    miR-126-5p/rno-
    miR-126*
    hsa-miR-298 FL
    hsa-miR-193a-5p FL
    hsa-miR-583 FL
    hsa-miR-143/mmu- FL
    miR-143/rno-miR-
    143
    hsa-miR-665 FL
    hsa-miR-505/rno- FL
    miR-505
    hsa-miR-199b-5p FL
    hsa-miR-28-3p/rno- FL
    miR-28*
    hsa-miR-422a FL
    hsa-miR-515-5p FL
    hsa-miR-455-3p FL
    hsa-miR-10a/mmu- FL
    miR-10a/rno-miR-
    10a-5p
    hsa-miR-300 FL
    ebv-miR-BART5 FL
    hsa-miR-10b/mmu- FL
    miR-10b/rno-miR-
    10b
    hsa-miR-212/mmu- FL
    miR-212/rno-miR-
    212
    hsa-miR-145/mmu- FL
    miR-145/rno-miR-
    145
    hsa-miR-187* FL
    ebv-miR-BHRF1-1 FL
    ebv-miR-BHRF1-2 FL
    hsa-miR-126/mmu- FL
    miR-126-3p/rno-
    miR-126
    hsa-miR- FL
    130b*/mmu-miR-
    130b*
    hsa-miR-326/mmu- FL
    miR-326/rno-miR-
    326
    mghv-miR-M1-2 FL
    kshv-miR-K12-6-3p FL
    hsa-miR-516b FL
    hsa-miR-519e* FL
    mghv-miR-M1-7-3p FL
    hsa-miR-629 FL
    hsa-miR-24-2*/mmu- FL
    miR-24-2*/rno-miR-
    24-2*
    hsa-miR-943 FL
    hsa-miR-124/mmu- FL
    miR-124/rno-miR-
    124
    hsa-miR-365/mmu- FL
    miR-365/rno-miR-
    365
    hsa-miR-493 FL
    hsa-miR-29c*/mmu- FL
    miR-29c*/rno-miR-
    29c*
    hsa-miR-602 FL
    hsa-miR-484/mmu- FL
    miR-484/rno-miR-
    484
    hsa-miR-483-3p FL
    hsa-miR-125b- FL
    2*/rno-miR-125b*
    hsa-miR-675 FL
    mghv-miR-M1-7-5p FL
    hsa-miR-152/mmu- FL
    miR-152/rno-miR-
    152
    hsa-miR-27a*/mmu- FL
    miR-27a*/rno-miR-
    27a*
    hsa-miR-542- FL
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    hsa-miR-100/mmu- FL
    miR-100/rno-miR-
    100
    hsa-miR-208a/mmu- FL
    miR-208a/rno-miR-
    208
    hsa-miR-766 FL
    hsa-miR-637 FL
    hsa-miR-519c- FL
    5p/hsa-miR-519b-
    5p/hsa-miR-
    523*/hsa-miR-
    518e*/hsa-miR-
    522*/hsa-miR-519a*
    hsa-miR-409- FL
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    hsa-miR-199a- FL
    3p/hsa-miR-199b-
    3p/mmu-miR-199a-
    3p/mmu-miR-
    199b/rno-miR-199a-
    3p
    hsa-miR- FL
    106b*/mmu-miR-
    106b*/rno-miR-
    106b*
    hsa-miR-130a/mmu- FL
    miR-130a/rno-miR-
    130a
    hsa-miR-645 FL
    hsa-miR-548d-5p FL
    hsa-miR-671- FL
    5p/mmu-miR-671-5p
    hsa-miR-574- FL
    3p/mmu-miR-574-3p
    hsa-miR-125b/mmu- FL
    miR-125b-5p/rno-
    miR-125b-5p
    hsa-miR-500* FL
    hsa-miR-425/mmu- FL
    miR-425/rno-miR-
    425
    ebv-miR-BART8* FL
    hsa-miR-377* FL
    hsa-miR-513a-3p FL
    hsa-miR-181a-2* FL
    hsa-miR-938 FL
    hsa-miR-155* FL
    hsa-miR-218- FL
    2*/mmu-miR-218-
    2*/rno-miR-218*
    hsa-miR-198 FL
    hsa-miR-151-3p FL
    hsa-miR-299-3p FL
    hcmv-miR-US25-1* FL
    hsa-miR-708/mmu- FL
    miR-708/rno-miR-
    708
    hsa-miR-659 FL
    hsa-miR-600 FL
    hsa-miR-601 FL
    hsa-miR-296- FL
    3p/mmu-miR-296-
    3p/rno-miR-296
    hsa-let-7b*/mmu-let- FL
    7b*/rno-let-7b*
    ebv-miR-BART6-3p FL
    hsa-miR-7-2* FL
    hsa-miR-9*/mmu- FL
    miR-9*/rno-miR-9*
    hsa-miR-509-3-5p FL
    hsa-miR-518b FL
    hsa-miR-183*/mmu- FL
    miR-183*
    hsa-miR-125b- FL
    1*/mmu-miR-125b-
    3p/rno-miR-125b-3p
    hsa-miR-183/mmu- FL
    miR-183/rno-miR-
    183
    hsa-miR-890 FL
    hsa-miR-153/mmu- FL
    miR-153/rno-miR-
    153
    hsa-miR-874/mmu- FL
    miR-874/rno-miR-
    874
    hsa-miR-220c FL
    hsa-miR-99b*/mmu- FL
    miR-99b*/rno-miR-
    99b*
    hsa-miR-193b* FL
    hsa-miR-629* FL
    hcmv-miR-UL148D FL
    ebv-miR-BART7* FL
    hsa-miR-99b/mmu- FL
    miR-99b/rno-miR-
    99b
    hsa-miR-206/mmu- FL
    miR-206/rno-miR-
    206
    hsa-miR-381/mmu- FL
    miR-381/rno-miR-
    381
    hsa-miR-194/mmu- FL
    miR-194/rno-miR-
    194
    hsa-miR-525-5p FL
    hsa-miR-193b FL
    hsa-miR-497/mmu- FL
    miR-497/rno-miR-
    497
    ebv-miR-BART18- FL
    3p
    hsa-miR-424 FL
    hsa-miR-553 FL
    hsa-let-7d*/mmu-let- FL
    7d*/rno-let-7d*
    hsa-miR-34c- FL
    5p/mmu-miR-
    34c/rno-miR-34c
    ebv-miR-BHRF1-3 FL
    kshv-miR-K12-6-5p FL
    hsa-miR-551a FL
    hsa-miR-195* FL
    hsa-miR-551b* FL
    hsa-miR-514 FL
    hsa-miR-552 FL
    hsa-miR-122* FL
    hsa-miR-92b/mmu- FL
    miR-92b/rno-miR-
    92b
    hsa-miR-22*/mmu- FL
    miR-22*/rno-miR-
    22*
    hsa-miR-635 FL
    kshv-miR-K12-1 FL
    hsa-miR-483-5p FL
    hsa-miR-340*/mmu- FL
    miR-340-3p/rno-
    miR-340-3p
    hsa-miR-615- FL
    3p/mmu-miR-615-3p
    hsa-miR-505* FL
    hsa-miR-622 FL
    hsa-miR-181b/mmu- FL
    miR-181b/rno-miR-
    181b
    hsa-miR-886-5p FL
    hsa-miR-885-5p FL
    hsa-miR-220b FL
    hsa-miR-524-5p FL
    hsa-miR-382/mmu- FL
    miR-382/rno-miR-
    382
    hsa-miR-744/mmu- FL
    miR-744
    hsv1-miR-H1 FL
    hsa-miR-526b FL
    hsa-miR-657 FL
    hsa-miR-130b/mmu- FL
    miR-130b/rno-miR-
    130b
    hsa-miR-181a/mmu- FL
    miR-181a/rno-miR-
    181a
    hsa-miR-301a/mmu- FL
    miR-301a/rno-miR-
    301a
    hsa-miR-490- FL
    3p/mmu-miR-490
    hsa-miR-485- FL
    3p/mmu-miR-485*
    hsa-miR-297/mmu- FL
    miR-297a
    hsa-miR-630 FL
    hsa-miR-877/mmu- FL
    miR-877/rno-miR-
    877
    kshv-miR-K12-5 FL
    hsa-miR-617 FL
    mghv-miR-M1-3 FL
    hsa-miR-920 FL
    hsa-miR-585 FL
    hsa-miR-374b* FL
    hsa-miR-215 FL
    hsa-miR-342- FL
    5p/mmu-miR-342-
    5p/rno-miR-342-5p
    hsa-miR-934 FL
    hsa-miR-575 FL
    hsa-miR-488 FL
    ebv-miR-BART16 FL
    hsa-miR-647 FL
    hsa-miR-138/mmu- FL
    miR-138/rno-miR-
    138
    hsa-miR-221* FL
    hsa-miR- FL
    200b*/mmu-miR-
    200b*
    hsa-miR-337-3p FL
    hsa-miR-922 FL
    hsa-miR-197/mmu- FL
    miR-197
    hsa-miR-96/mmu- FL
    miR-96/rno-miR-96
    hsa-miR-518a-3p FL
  • TABLE 29
    Predictor microRNAs that distinguish Burkitt lymphoma
    from Hodgkin's lymphoma
    Higher
    CLL vs HL in
    hsa-miR-32/mmu-miR- CLL
    32/rno-miR-32
    hsa-miR-30e*/mmu-miR- CLL
    30e*/rno-miR-30e*
    hsa-let-7g/mmu-let-7g CLL
    hsa-miR-144/mmu-miR- CLL
    144/rno-miR-144
    hsa-miR-140-5p/mmu- CLL
    miR-140/rno-miR-140
    hsa-miR-19a/mmu-miR- CLL
    19a/rno-miR-19a
    hsa-miR-154/mmu-miR- CLL
    154/rno-miR-154
    hsa-miR-150/mmu-miR- CLL
    150/rno-miR-150
    hsa-miR-28-5p/mmu- CLL
    miR-28/rno-miR-28
    hsa-miR-363/mmu-miR- CLL
    363/rno-miR-363
    hsa-miR-101/mmu-miR- CLL
    101a/rno-miR-101a
    hsa-miR-299-5p/mmu- CLL
    miR-299*/rno-miR-299
    hsa-miR-768-5p CLL
    hsa-miR-19b/mmu-miR- CLL
    19b/rno-miR-19b
    hsa-miR-30e/mmu-miR- CLL
    30e/rno-miR-30e
    hsa-miR-20b/mmu-miR- CLL
    20b/rno-miR-20b-5p
    hsa-miR-374a CLL
    hsa-let-7f/mmu-let-7f/rno- CLL
    let-7f
    hsa-miR-335/mmu-miR- CLL
    335-5p/rno-miR-335
    hsa-miR-142-5p/mmu- CLL
    miR-142-5p/rno-miR-142-
    5p
    hsa-miR-486-5p/mmu- CLL
    miR-486
    hsa-miR-33a/mmu-miR- CLL
    33/rno-miR-33
    hsa-miR-30b/mmu-miR- CLL
    30b/rno-miR-30b-5p
    hsa-miR-768-3p CLL
    hsa-miR-668/mmu-miR- CLL
    668
    hsa-miR-15b/mmu-miR- CLL
    15b/rno-miR-15b
    hsa-miR-196a*/mmu- CLL
    miR-196a*/rno-miR-196a*
    hsa-miR-140-3p/mmu- CLL
    miR-140*/rno-miR-140*
    hsa-miR-29b/mmu-miR- CLL
    29b/rno-miR-29b
    hsa-miR-29c/mmu-miR- CLL
    29c/rno-miR-29c
    hsa-miR-186/mmu-miR- CLL
    186/rno-miR-186
    hsa-miR-106a CLL
    hsa-miR-26a/mmu-miR- CLL
    26a/rno-miR-26a
    hsa-miR-106b/mmu-miR- CLL
    106b/rno-miR-106b
    hsa-miR-17/mmu-miR- CLL
    17/rno-miR-17-5p/rno-
    miR-17
    hsa-miR-191/mmu-miR- CLL
    191/rno-miR-191
    hsa-miR-20a/mmu-miR- CLL
    20a/rno-miR-20a
    hsa-miR-30c/mmu-miR- CLL
    30c/rno-miR-30c
    hsa-miR-26b/mmu-miR- CLL
    26b/rno-miR-26b
    hsa-miR-147 CLL
    hsa-miR-15a/mmu-miR- CLL
    15a
    hsa-miR-30d/mmu-miR- CLL
    30d/rno-miR-30d
    hsa-miR-199a-5p/mmu- CLL
    miR-199a-5p/rno-miR-
    199a-5p
    hsa-miR-29a/mmu-miR- CLL
    29a/rno-miR-29a
    hsa-miR-223/mmu-miR- CLL
    223/rno-miR-223
    hsa-miR-30a/mmu-miR- CLL
    30a/rno-miR-30a
    hsa-miR-16/mmu-miR- CLL
    16/rno-miR-16
    hsa-miR-451/mmu-miR- CLL
    451/rno-miR-451
    hsa-miR-24-1*/mmu-miR- CLL
    24-1*/rno-miR-24-1*
    hsa-miR-550 CLL
    hsa-miR-342-3p/mmu- CLL
    miR-342-3p/rno-miR-342-
    3p
    hsa-miR-195/mmu-miR- CLL
    195/rno-miR-195
    hsa-miR-801/mmu-miR- CLL
    801
    hsa-miR-541* CLL
    hsa-let-7i/mmu-let-7i/rno- CLL
    let-7i
    hsa-miR-155 CLL
    hsa-miR-185/mmu-miR- CLL
    185/rno-miR-185
    hsa-miR-891a CLL
    hsa-miR-138-1*/mmu- CLL
    miR-138*/rno-miR-138*
    hsa-miR-27b/mmu-miR- CLL
    27b/rno-miR-27b
    hsa-miR-361-5p/mmu- CLL
    miR-361/rno-miR-361
    hsa-miR-129* CLL
    hsa-miR-638 CLL
    hsa-miR-34b/mmu-miR- CLL
    34b-3p
    hsa-miR-107/mmu-miR- CLL
    107/rno-miR-107
    hsa-miR-549 CLL
    hsa-miR-888* CLL
    hsa-miR-423-3p/mmu- CLL
    miR-423-3p/rno-miR-423
    hsa-let-7e/mmu-let- HL
    7e/rno-let-7e
    hsa-miR-125a-5p/mmu- HL
    miR-125a-5p/rno-miR-
    125a-5p
    hsa-miR-576-3p HL
    hsa-miR-513a-5p HL
    ebv-miR-BART17-5p HL
    hsa-miR-185/mmu-miR- HL
    185/rno-miR-185
    hsa-miR-921 HL
    hsa-miR-518c* HL
    hsa-miR-520d-5p HL
    hsa-miR-939 HL
    hsa-miR-634 HL
    hsa-miR-491-3p HL
    ebv-miR-BART2-3p HL
    hsa-miR-30c-2*/mmu- HL
    miR-30c-2*/rno-miR-30c-
    2*
    hsa-miR-765 HL
    hsa-miR-923 HL
    hsa-miR-620 HL
    hsa-miR-933 HL
    hsa-miR-143/mmu-miR- HL
    143/rno-miR-143
    hsa-miR-494/mmu-miR- HL
    494/rno-miR-494
    hsa-miR-665 HL
    hsa-miR-642 HL
    hsa-miR-126*/mmu-miR- HL
    126-5p/rno-miR-126*
    hsa-miR-658 HL
    hsa-miR-149* HL
    hsa-miR-30b* HL
    mghv-miR-M1-4 HL
    hsa-miR-99a/mmu-miR- HL
    99a/rno-miR-99a
    hsa-miR-193a-5p HL
    hsa-miR-498 HL
    hsa-miR-628-3p HL
    hsa-miR-185* HL
    hsa-miR-371-5p HL
    hsa-miR-199b-5p HL
    hsa-miR-126/mmu-miR- HL
    126-3p/rno-miR-126
    hsa-miR-503 HL
    hsa-miR-10a/mmu-miR- HL
    10a/rno-miR-10a-5p
    hsa-miR-300 HL
    hsa-miR-583 HL
    hsa-miR-518a-5p/hsa- HL
    miR-527
    hsa-miR-10b/mmu-miR- HL
    10b/rno-miR-10b
    hsa-miR-145/mmu- HL
    miR-145/rno-miR-
    145
    hsa-miR-128/mmu- HL
    miR-128/rno-miR-
    128
    hsa-miR-532- HL
    5p/mmu-miR-532-
    5p/rno-miR-532-5p
    hsa-miR-143* HL
    hsa-miR-28-3p/rno- HL
    miR-28*
    hsa-miR- HL
    130b*/mmu-miR-
    130b*
    hsa-miR-505/rno- HL
    miR-505
    hsa-miR-25* HL
    hsa-miR-574- HL
    3p/mmu-miR-574-3p
    hsa-miR-455-3p HL
    kshv-miR-K12-3 HL
    hsa-miR-516b HL
    kshv-miR-K12-8 HL
    hsa-miR-502-3p HL
    kshv-miR-K12-6-3p HL
    hsa-miR-129- HL
    5p/mmu-miR-129-
    5p/rno-miR-129
    hsa-miR-515-5p HL
    hsa-miR-199a- HL
    3p/hsa-miR-199b-
    3p/mmu-miR-199a-
    3p/mmu-miR-
    199b/rno-miR-199a-
    3p
    hsa-miR-149/mmu- HL
    miR-149
    hsa-miR-889 HL
    hsa-miR-637 HL
    hsa-miR-600 HL
    hsa-miR-151-3p HL
    hsa-miR-656 HL
    hsa-miR-497/mmu- HL
    miR-497/rno-miR-
    497
    hsa-miR-152/mmu- HL
    miR-152/rno-miR-
    152
    hsa-miR-100/mmu- HL
    miR-100/rno-miR-
    100
    hsa-miR-425/mmu- HL
    miR-425/rno-miR-
    425
    hsa-miR-145*/mmu- HL
    miR-145*
    hsa-miR-365/mmu- HL
    miR-365/rno-miR-
    365
    hsa-miR-422a HL
    hcmv-miR-UL70-3p HL
    hsa-miR-27a*/mmu- HL
    miR-27a*/rno-miR-
    27a*
    hsa-miR-194/mmu- HL
    miR-194/rno-miR-
    194
    hsa-miR-548d-5p HL
    hsa-miR-187* HL
    hsa-miR-323- HL
    3p/mmu-miR-323-
    3p/rno-miR-323
    hsa-miR-708/mmu- HL
    miR-708/rno-miR-
    708
    hsa-miR-29c*/mmu- HL
    miR-29c*/rno-miR-
    29c*
    hsa-miR-513a-3p HL
    hsa-miR-595 HL
    hsa-miR-483-3p HL
    hsa-miR-330- HL
    5p/mmu-miR-
    330/rno-miR-330
    hsa-miR-519e* HL
    hsa-miR-509-3p HL
    hsa-miR-328/mmu- HL
    miR-328/rno-miR-
    328
    hsa-miR-373* HL
    hsa-miR-96/mmu- HL
    miR-96/rno-miR-96
    hsa-miR-215 HL
    hsa-miR-589 HL
    hsa-miR-34c- HL
    5p/mmu-miR-
    34c/rno-miR-34c
    hsa-miR-125b/mmu- HL
    miR-125b-5p/rno-
    miR-125b-5p
    hsa-miR-130a/mmu- HL
    miR-130a/rno-miR-
    130a
    hsa-miR-519c- HL
    5p/hsa-miR-519b-
    5p/hsa-miR-
    523*/hsa-miR-
    518e*/hsa-miR-
    522*/hsa-miR-519a*
    mghv-miR-M1-7-5p HL
    hsa-miR-516a-5p HL
    hsa-miR-424 HL
    hsa-miR-17*/rno- HL
    miR-17-3p
    hsa-miR-296- HL
    5p/mmu-miR-296-
    5p/rno-miR-296*
    hsa-miR-550* HL
    hsa-miR-210/mmu- HL
    miR-210/rno-miR-
    210
    hsa-miR-92b/mmu- HL
    miR-92b/rno-miR-
    92b
    hsa-miR-548b-3p HL
    hsa-miR-652/mmu- HL
    miR-652/rno-miR-
    652
    hsa-miR-138/mmu- HL
    miR-138/rno-miR-
    138
    hsa-miR-194* HL
    hsa-miR-23a*/rno- HL
    miR-23a*
    hsa-miR-153/mmu- HL
    miR-153/rno-miR-
    153
    hsa-miR-586 HL
    hsa-miR-137/mmu- HL
    miR-137/rno-miR-
    137
    hsa-miR-610 HL
    hsa-miR-381/mmu- HL
    miR-381/rno-miR-
    381
    hsa-miR-936 HL
    hsa-miR-744/mmu- HL
    miR-744
    ebv-miR-BART5 HL
    ebv-miR-BHRF1-1 HL
    hsa-miR-21* HL
    hsa-miR-576-5p HL
    mghv-miR-M1-6 HL
    hsa-miR-193b HL
    hsa-miR-10a*/mmu- HL
    miR-10a*/rno-miR-
    10a-3p
    hsa-miR-524-5p HL
    hsa-miR-452 HL
    hsa-miR-345 HL
    hsa-miR-7-2* HL
    hsa-miR-409- HL
    5p/mmu-miR-409-
    5p/rno-miR-409-5p
    hsa-miR-557 HL
    hsa-miR-181a/mmu- HL
    miR-181a/rno-miR-
    181a
    hsa-miR-22*/mmu- HL
    miR-22*/rno-miR-22*
    hsa-miR-922 HL
    hsa-miR-92b* HL
    hsa-miR-938 HL
    hsa-miR-526a/hsa- HL
    miR-520c-5p/hsa-
    miR-518d-5p
    hsa-miR-526b* HL
    ebv-miR-BHRF1-2 HL
    hiv1-miR-H1 HL
    hsa-miR-623 HL
    mghv-miR-M1-2 HL
    mghv-miR-M1-7-3p HL
    hsa-miR-519e HL
    hsa-miR-650 HL
    hsa-miR-766 HL
    hsa-miR-602 HL
    hsa-miR-425*/mmu- HL
    miR-425*
    hsa-miR- HL
    135a*/mmu-miR-
    135a* HL
    hsa-miR-612 HL
    hsa-miR-212/mmu- HL
    miR-212/rno-miR-
    212
    hsa-miR-125b- HL
    2*/rno-miR-125b*
    hcmv-miR-UL112 HL
    hsa-miR-374b*
    hsa-miR-886-5p HL
    hsa-miR-500 HL
    hsa-miR-502-5p HL
    ebv-miR-BART18- HL
    3p
    hsa-miR-198 HL
    hsa-miR-500* HL
    hsa-miR-342- HL
    5p/mmu-miR-342-
    5p/rno-miR-342-5p
    hsa-miR-124*/mmu- HL
    miR-124*/rno-miR-
    124*
    hsa-miR-30c- HL
    1*/mmu-miR-30c-
    1*/rno-miR-30c-1*
    hsa-miR-220c HL
    hsa-miR-376a* HL
    hsa-miR-640 HL
    hcmv-miR-UL148D HL
    hsa-miR-659 HL
    hsa-miR-934 HL
    hsa-miR-125a- HL
    3p/mmu-miR-125a-
    3p/rno-miR-125a-3p
    hsa-miR-885-5p HL
    hsa-miR-24- HL
    2*/mmu-miR-24-
    2*/rno-miR-24-2*
    hsa-miR-484/mmu- HL
    miR-484/rno-miR-
    484
    hsa-miR- HL
    106b*/mmu-miR-
    106b*/rno-miR-
    106b*
    hsa-miR-505* HL
    hsa-let-7b*/mmu-let- HL
    7b*/rno-let-7b*
    hsa-miR-302c* HL
    hsa-miR-542- HL
    5p/mmu-miR-542-
    5p/rno-miR-542-5p
    hsv1-miR-H1 HL
    mghv-miR-M1-3 HL
    hsa-miR-183/mmu- HL
    miR-183/rno-miR-
    183
    hsa-miR-122* HL
    hsa-miR-183*/mmu- HL
    miR-183*
    hsa-miR-675 HL
    hsa-miR-99b/mmu- HL
    miR-99b/rno-miR-
    99b
    hsa-miR-874/mmu- HL
    miR-874/rno-miR-
    874
    ebv-miR-BART20- HL
    3p
    hsa-miR-483-5p HL
    hsa-miR-671- HL
    5p/mmu-miR-671-5p
    hsa-miR-629 HL
    hsa-miR-553 HL
    hsa-let-7d*/mmu-let- HL
    7d*/rno-let-7d*
    hsa-miR-601 HL
    hsa-miR-645 HL
    hsa-miR-920 HL
    hsa-miR-525-5p HL
    hsa-miR-221* HL
    hsa-miR-890 HL
    hsa-miR-492 HL
    hsa-miR-629* HL
    hsa-miR-635 HL
    hsa-miR-130b/mmu- HL
    miR-130b/rno-miR-
    130b
    hsa-miR-197/mmu- HL
    miR-197
    hsa-miR-654-5p HL
    hsa-miR-518b HL
    hsa-miR-382/mmu- HL
    miR-382/rno-miR-
    382
    hsa-miR-584 HL
    hsa-miR-99b*/mmu- HL
    miR-99b*/rno-miR-
    99b*
    hsa-miR-630 HL
    hsa-miR-490-5p HL
    hsa-miR-663 HL
    hsa-miR-337-3p HL
    hsa-miR-9*/mmu- HL
    miR-9*/rno-miR-9*
    hsa-miR-202 HL
    ebv-miR-BART16 HL
    ebv-miR-BART9* HL
    hsa-miR-193b* HL
    ebv-miR-BART8* HL
    hsa-miR-206/mmu- HL
    miR-206/rno-miR-
    206
    hcmv-miR-US25-1* HL
    hsa-miR-514 HL
    kshv-miR-K12-6-5p HL
    hsa-miR-488 HL
    hsa-miR-508-5p HL
    hsa-miR-551b* HL
    hsa-miR-377* HL
    ebv-miR-BART6-3p HL
    hsa-miR-181b/mmu- HL
    miR-181b/rno-miR-
    181b
    hsa-miR-526b HL
    hsa-miR-622 HL
    kshv-miR-K12-1 HL
    hsa-miR-485- HL
    3p/mmu-miR-485*
    hsa-miR-490- HL
    3p/mmu-miR-490
    hsa-miR-125b- HL
    1*/mmu-miR-125b-
    3p/rno-miR-125b-3p
    hsa-miR-124/mmu- HL
    miR-124/rno-miR-
    124
    hsa-miR-657 HL
    ebv-miR-BHRF1-3 HL
    hsa-miR-542- HL
    3p/mmu-miR-542-
    3p/rno-miR-542-3p
    kshv-miR-K12-5 HL
    hsa-miR-943 HL
    hsa-miR-551a HL
    hsa-miR-297/mmu- HL
    miR-297a
    hsa-miR-296- HL
    3p/mmu-miR-296-
    3p/rno-miR-296
    hsa-miR-617 HL
    hsa-miR-195* HL
    hsa-miR-575 HL
    hsa-miR-208a/mmu- HL
    miR-208a/rno-miR-
    208
    hsa-miR-647 HL
    hsa-miR-509-3-5p HL
    hsa-miR-340*/mmu- HL
    miR-340-3p/rno-
    miR-340-3p
    hsa-miR-220b HL
    hsa-miR- HL
    200b*/mmu-miR-
    200b*
    hsa-miR-585 HL
    hsa-miR-877/mmu- HL
    miR-877/rno-miR-
    877
    hsa-miR-326/mmu- HL
    miR-326/rno-miR-
    326
    ebv-miR-BART7* HL
    hsa-miR-615- HL
    3p/mmu-miR-615-3p
    hsa-miR-433/mmu- HL
    miR-433/rno-miR-
    433
    hsa-miR-338- HL
    5p/mmu-miR-338-
    5p/rno-miR-338*
    hsa-miR-299-3p HL
    hsa-miR-518a-3p HL
    hsa-miR-181a-2* HL
    hsa-miR-552 HL
  • TABLE 30
    Predictor microRNAs that distinguish follicular lymphoma
    from Hodgkin's lymphoma
    Higher
    FL vs HL in
    hsa-miR-301a/mmu-miR- FL
    301a/rno-miR-301a
    kshv-miR-K12-7 FL
    hsa-miR-96/mmu-miR- FL
    96/rno-miR-96
    hsa-miR-151-5p/mmu- FL
    miR-151-5p/rno-miR-151
    hsa-miR-28-5p/mmu-miR- FL
    28/rno-miR-28
    hsa-miR-302a/mmu-miR- FL
    302a
    hsa-miR-215 FL
    hsa-miR-15b/mmu-miR- FL
    15b/rno-miR-15b
    hsa-miR-29b/mmu-miR- FL
    29b/rno-miR-29b
    hsa-miR-138/mmu-miR- FL
    138/rno-miR-138
    hsa-miR-363/mmu-miR- FL
    363/rno-miR-363
    hsa-miR-142-5p/mmu- FL
    miR-142-5p/rno-miR-142-
    5p
    hsa-miR-19a/mmu-miR- FL
    19a/rno-miR-19a
    hsa-miR-497/mmu-miR- FL
    497/rno-miR-497
    hsa-miR-144* FL
    hsa-miR-16/mmu-miR- FL
    16/rno-miR-16
    hsa-miR-138-1*/mmu- FL
    miR-138*/rno-miR-138*
    hsa-miR-768-5p FL
    hsa-miR-30c/mmu-miR- FL
    30c/rno-miR-30c
    hsa-miR-129* FL
    hsa-miR-801/mmu-miR- FL
    801
    hsa-miR-34b/mmu-miR- FL
    34b-3p
    hsa-miR-363*/rno-miR- FL
    363*
    hsa-miR-20b* FL
    hsa-miR-550 FL
    hsa-miR-600 FL
    hsa-miR-196a*/mmu- FL
    miR-196a*/rno-miR-196a*
    hsa-miR-574-3p/mmu- FL
    miR-574-3p
    hsa-miR-620 FL
    hsa-miR-331-3p/mmu- FL
    miR-331-3p/rno-miR-331
    hsa-let-7e/mmu-let- FL
    7e/rno-let-7e
    hsa-miR-524-5p FL
    hsa-miR-197/mmu-miR- FL
    197
    hsa-miR-24-1*/mmu-miR- FL
    24-1*/rno-miR-24-1*
    hsa-miR-519e* HL
    hsa-miR-628-3p HL
    mghv-miR-M1-7-5p HL
    hsa-miR-498 HL
    hsa-miR-525-5p HL
    hsa-miR-520d-5p HL
    hsa-miR-551b* HL
    hsa-miR-340*/mmu- HL
    miR-340-3p/rno-
    miR-340-3p
    hsa-miR-889 HL
    hsa-miR-494/mmu- HL
    miR-494/rno-miR-
    494
    hsa-miR-874/mmu- HL
    miR-874/rno-miR-
    874
    hsa-miR-30c- HL
    2*/mmu-miR-30c-
    2*/rno-miR-30c-2*
    hsa-miR-183*/mmu- HL
    miR-183*
    hsa-miR-25* HL
    hsa-miR-513a-5p HL
    hsa-miR-198 HL
    hsa-miR-659 HL
    mghv-miR-M1-4 HL
    hsa-miR-129- HL
    5p/mmu-miR-129-
    5p/rno-miR-129
    ebv-miR-BART13 HL
    hsa-miR-193b* HL
    hsa-miR-422a HL
    hsa-miR-503 HL
    kshv-miR-K12-3 HL
    hsa-miR-766 HL
    hsa-miR-516a-5p HL
    hsa-miR-125b- HL
    1*/mmu-miR-125b-
    3p/rno-miR-125b-3p
    hsa-miR-149* HL
    ebv-miR-BART6-3p HL
    ebv-miR-BART19-3p HL
    hsa-miR-671- HL
    5p/mmu-miR-671-5p
    ebv-miR-BART8* HL
    hsa-miR-509-3-5p HL
    hsa-miR-602 HL
    ebv-miR-BHRF1-1 HL
    mghv-miR-M1-7-3p HL
    mghv-miR-M1-2 HL
    hsa-miR-675 HL
    ebv-miR-BHRF1-2 HL
    hsa-miR-145*/mmu- HL
    miR-145*
    hsa-miR-296-5p/mmu- HL
    miR-296-5p/rno-miR-
    296*
    hsa-miR-17*/rno-miR- HL
    17-3p
    hsa-miR-452 HL
    hsa-miR-943 HL
    hsa-miR-326/mmu-miR- HL
    326/rno-miR-326
    hsa-miR-652/mmu-miR- HL
    652/rno-miR-652
    hsa-miR-623 HL
    hsa-miR-194* HL
    hsa-miR-557 HL
    hsa-miR-125a-3p/mmu- HL
    miR-125a-3p/rno-miR-
    125a-3p
    hsa-miR-425*/mmu- HL
    miR-425*
    hsa-miR-10a*/mmu- HL
    miR-10a*/rno-miR-10a-
    3p
    hsa-miR-323-3p/mmu- HL
    miR-323-3p/rno-miR-
    323
    hsa-miR-519e HL
    hsa-miR-502-5p HL
    hsa-miR-124*/mmu- HL
    miR-124*/rno-miR-124*
    hsa-miR-345 HL
    hsa-miR-584 HL
    hsa-miR-654-5p HL
    hsa-miR-331-5p/mmu- HL
    miR-331-5p
    hsa-miR-650 HL
    hsa-miR-202 HL
    hsa-miR-548b-3p HL
    hsa-miR-492 HL
    hsa-miR-135a*/mmu- HL
    miR-135a*
    ebv-miR-BART20-3p HL
    hsa-miR-586 HL
    hsa-miR-338-5p/mmu- HL
    miR-338-5p/rno-miR-
    338*
    hsa-miR-92b* HL
    hiv1-miR-H1 HL
    hsa-miR-508-5p HL
    hsa-miR-542-5p/mmu- HL
    miR-542-5p/rno-miR-
    542-5p
    hsa-miR-490-5p HL
    hsa-miR-663 HL
    hsa-miR-433/mmu-miR- HL
    433/rno-miR-433

Claims (30)

1. A composition comprising an isolated nucleic acid molecule having at least 80% sequence identity to any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof.
2. The composition of claim 1, wherein the isolated nucleic acid molecule is a nucleic acid molecule having at least 90% sequence identity to any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof.
3. (canceled)
4. The composition of claim 1, wherein the isolated nucleic acid molecule is a nucleic acid molecule comprising any one of SEQ ID NOs: 763-1350 or 1565 or a complementary sequence thereof.
5. The composition of claim 1, wherein the isolated nucleic acid molecule is a miRNA precursor molecule having the sequence of SEQ ID NOs: 763-1350 or 1565, or a DNA molecule coding the miRNA.
6. The composition of claim 1, wherein the isolated nucleic acid molecule is either single-stranded or at least partially double-stranded.
7. (canceled)
8. The composition of claim 1, wherein the isolated nucleic acid molecule is selected from RNA or DNA molecules.
9. The composition of claim 1, wherein the isolated nucleic acid molecule is a cDNA that corresponds to any one of SEQ ID NOs: 763-1350 or 1565.
10. The composition of claim 1, wherein the isolated nucleic acid molecule comprises at least one modified nucleotide analog.
11. The composition of claim 1, further comprising a carrier or vehicle, wherein the isolated nucleic acid molecule is suitable as a marker or modulator of a B cell malignancy, and wherein the carrier or vehicle is a pharmaceutically acceptable carrier or vehicle suitable for diagnostic or therapeutic applications.
12-14. (canceled)
15. The composition of claim 1, wherein the isolated nucleic acid molecule is operably linked to a recombinant expression vector.
16. A cell comprising the recombinant expression vector of claim 15.
17. (canceled)
18. (canceled)
19. A method of identifying a B cell malignancy in a subject comprising determining the level of expression of at least one microRNA in a sample comprising a B cell taken from the subject relative the level of expression of the at least one microRNA in a control sample, wherein the at least one microRNA is selected from the microRNAs listed in any one of Tables 4 and 7 to 35.
20. (canceled)
21. The method of claim 19, wherein the B cell malignancy is one of at least two potential B cell malignancies, wherein at least two of the potential B cell malignancies are derived from different B cell stages.
22. (canceled)
23. The method of claim 19, wherein the B cell malignancy is selected from chronic lymphocytic leukemia, follicular lymphoma, Hodgkin's lymphoma, activated B-cell diffuse large B cell lymphoma (DLBCL), germinal center-like DLBCL, and Burkitt lymphoma.
24-34. (canceled)
35. A kit comprising one or more sequences selected from a group consisting of
(a) at least one primer sequence that can detect any one of SEQ ID NOs: 763-1350 or 1565, or a combination thereof;
(b) at least one isolated nucleic acid molecule having a sequence of any one of SEQ ID NOs: 1351-1564;
(c) the isolated nucleic acid molecule of claim 1; and
(d) any combination of (a)-(c).
36. (canceled)
37. The kit of claim 35, wherein (a) further comprises enzymes and reagents that are adequate for performing an RT-PCR reaction.
38-41. (canceled)
42. The method of claim 19, further comprising determining whether the B cell malignancy in the sample is Burkitt lymphoma, activated B cell-like diffuse large B cell lymphoma (DLBCL), or germinal center-like DLBCL, comprising determining the level of expression of at least one microRNA in the sample relative to the level of expression of the at least one microRNA in the control sample, wherein the at least one microRNA is selected from the microRNAs listed in Table 7, column “GCBvsBL”; Table 7, column “GCBvsABC”; Table 8, column “ABCvsBL”; Table 10, column “BL miRNA list”; Table 10, column “GCB miRNA list”; Table 11; Table 14, column “BL High”; Table 14, column “ABC High”; Table 14, column “GCB High”; Table 32; or Table 35.
43. The method of claim 42, comprising determining the level of expression of at least one microRNA selected from the microRNAs listed in Table 10, column “BL miRNA list”, and Table 14, column “BL High”; determining the level of expression of at least one microRNA selected from the microRNAs listed in Table 11 and Table 14, column “ABC High”; and determining the level of expression of at least one microRNA selected from the microRNAs listed in Table 10, column “GCB miRNA list”, and Table 14, column “GCB High”.
44. The method of claim 43, wherein at least one microRNA is listed in only one column selected from the columns labeled “GCBvsBL” or “GCBvsABC” in Table 7 or “ABCvsBL” in Table 8.
45. The method of claim 42, wherein at least one microRNA is listed in no more than two columns selected from the columns labeled “GCBvsBL” or “GCBvsABC” in Table 7 or “ABCvsBL” in Table 8.
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