WO2024159070A1

WO2024159070A1 - Assessing and treating mammals having polyps

Info

Publication number: WO2024159070A1
Application number: PCT/US2024/013057
Authority: WO
Inventors: Lisa A. Boardman
Original assignee: Mayo Foundation For Medical Education And Research
Priority date: 2023-01-26
Filing date: 2024-01-26
Publication date: 2024-08-02

Abstract

This document relates to methods and materials for assessing and/or treating mammals (e.g., humans) having one or more polyps (e.g., one or more colon polyps). For example, methods and materials that can be used for determining if a polyp (e.g., a colon polyp) within a mammal (e.g., a human) is malignant polyp and/or is likely to recur are provided. This document also provides methods and materials for treating a mammal having one or more polyps (e.g., one or more colon polyps).

Description

Attorney Docket No.07039-2155WO1 / 2022-250 ASSESSING AND TREATING MAMMALS HAVING POLYPS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Patent Application Serial No.63/441,360, filed on January 26, 2023. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application. STATEMENT REGARDING FEDERAL FUNDING This invention was made with government support under CA170357 awarded by the National Institutes of Health. The government has certain rights in the invention TECHNICAL FIELD This document relates to methods and materials for assessing and/or treating mammals (e.g., humans) having one or more polyps (e.g., one or more colon polyps). For example, methods and materials provided herein can be used to determine if a polyp (e.g., a colon polyp) within a mammal (e.g., a human) is or is likely to become a malignant polyp and/or is likely to recur. This document also provides methods and materials for treating a mammal having one or more polyps (e.g., one or more colon polyps). BACKGROUND INFORMATION Colorectal cancer (CRC) develops through progressive accumulation of molecular alterations beginning with abnormal growth of the colon epithelium, which over time can transform to an adenoma (polyp) and then potentially cancer. The current understanding of CRC development and progression is that there are interactions between somatic and germline genetic, transcriptional, epigenetic, immune and other regulatory events that drive malignant transformation (Cancer Genome Atlas, Nature, 487:330-7 (2012); Fearon, Ann. Rev. Pathol., 6:479-507 (2011); Fearon et al., Cell, 61:759-67 (1990); and Wood et al., Science, 318:1108-13 (2007)). This information has been characterized temporally in the adenoma-carcinoma sequence from unmatched cases, and it still not known why one polyp develops into cancer while another identical one does not (Fearon, Ann. Rev. Pathol., 6:479- 507 (2011); Chakradhar, Nature, 521:S16 (2015); Hershkovitz et al., Hum. Pathol., 45:1866- Attorney Docket No.07039-2155WO1 / 2022-250 71 (2014); Jones et al., Proc. Natl. Acad. Sci. USA, 105:4283-8 (2008); Chen et al., Cell, 184:6262-6280 e26 (2021); and Sedivy et al., Br. J. Cancer, 82:1276-82 (2000)). The keystone of preventing CRC requires screening for polyps and successfully removing these lesions. Currently, determining whether a polyp may transform to cancer can be made based on the physical features of the polyp such as size, histology, and degree of dysplasia. Up to 60% of patients who undergo screening colonoscopy will have polyps that will recur and therefore require repeated surveillance and removal (Zachariah et al., Am. J. Gastroenterol., 115:138-144 (2020); and Harrington et al., AMIA Jt Summits Transl. Sci. Proc., 2020:211–220 (2020)). Despite this repeated surveillance, 3% of polyps may still transform to cancer (Mouchli et al., World J. Gastroenterol., 24:905-916 (2018)), and 48% of advanced adenomas recur at the site where the index (original) polyp was removed within one to three years of index polypectomy (Khashab et al., Gastrointest. Endosc., 70:344-9 (2009); Klein et al., Gastroenterology, 156:604-613 e3 (2019); Laiyemo et al., Digestion, 87:141-6 (2013); Seitz et al., Endoscopy, 35:S41-4 (2003); Weinberg, Gastrointest. Endosc., 70:350-2 (2009); and Winawer et al., CA Cancer. J. Clin., 56:143-59 (2006)). SUMMARY There is a need to be able to identify polyps that are likely to progress to cancer, and to offer high-risk patients early therapy, while sparing low risk patients from the risk of toxicity from therapeutic intervention. This document provides methods and materials for assessing and/or treating mammals (e.g., humans) having one or more polyps (e.g., one or more colon polyps). For example, the methods and materials provided herein can be used to determine if a polyp (e.g., a polyp within a mammal having one or more polyps) is or is likely to become a malignant polyp and/or if a polyp (e.g., a polyp within a mammal having one or more polyps) is likely to recur. In some cases, a molecular profile of a polyp can be used to determine if that polyp is or is likely to become a malignant polyp and/or if that polyp is likely to recur. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps can be assessed to determine if a polyp (e.g., a polyp within a mammal having one or more polyps) is or is likely to become a malignant polyp and/or is likely to recur based, at least in part, on the molecular profile of the polyp. This document also Attorney Docket No.07039-2155WO1 / 2022-250 provides methods and materials for treating a mammal having one or more polyps (e.g., one or more colorectal polyps). For example, a mammal (e.g., a human) having one or more polyps (e.g., one or more colorectal polyps) can be administered one or more treatments that are selected based, at least in part, on the molecular profile of the polyp. As demonstrated herein, the molecular profile of a polyp can distinguish whether that polyp is a benign polyp or a malignant polyp. For example, a polyp is or is likely to become malignant can have a molecular profile that includes differential expression of ADAMTS4, THBS2, SERPINE1, FAP, CYR61, SOX11, CXCL13, SFRP2, and VIP, and/or overexpression of TERT (e.g., resulting in changes in telomere structure such as telomere length and telomere content), and, optionally, includes altered levels of natural killer cell (NKCs) in the resting phase, one or more chromosomal rearrangements (e.g., a genomic duplication (DUP), a genomic deletion (DEL), a genomic insertion/deletion (INDEL)), loss of heterozygosity (LOH), and/or increased copy number variation (CNV)) as compared to polyps that are clinically indistinguishable (e.g., by endoscopic and/or histological appearance) and remain benign. Also as demonstrated herein, the molecular profile of a polyp can distinguish whether that polyp is likely to recur. In some cases, the molecular profile of a polyp can distinguish whether that polyp is likely to recur in the same location from which the polyp was removed from a mammal (e.g., a human). For example, a polyp that is likely to recur can have a molecular profile that includes differential expression of TPRG1, LY6G6C, DUSP4, ZIC5, CYP1A1, DMKN, and IGLL5, and, optionally, includes a mutated KRAS and/or one or more changes in genetic content (e.g., a genomic DEL and/or LOH) as compared to polyps that are not likely to recur. These findings provide a resource of molecular distinctions between polyps with and without cancer, which have the potential to enhance the diagnosis, risk assessment and management of polyps. Having the ability to determine risk whether a polyp is or is likely to become a malignant polyp and/or is likely to recur provides a unique and unrealized opportunity to provide personalized treatment plans for patients having one or more polyps (e.g., one or more colon polyps). For example, when one or more polyps within a patient are identified as being or as likely to become malignant and/or as likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp(s)), therapy can be initiated early, rather than waiting to treat the patient until after a cancer has developed. For example, when Attorney Docket No.07039-2155WO1 / 2022-250 one or more polyps within a patient are identified as not being or not likely to become malignant and/or as not likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp(s)), a patient having one or more polyps (e.g., one or more colon polyps) can undergo less frequent monitoring (e.g., less frequent surveillance colonoscopies) rather than being subjected to unnecessary treatments. In general, one aspect of this document features methods for assessing a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining (i) if a sample from a mammal having one or o more colon polyps contains the presence or absence of at least one of (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide, and (ii) if the sample contains the presence or absence of at least one of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of natural killer cells (NKCs) in the resting phase, (12) an increased frequency of genomic duplications (DUPs), (13) an increased frequency of genomic deletions (DELs), (14) an increased frequency of loss of heterozygosity (LOH), and (15) a higher telomere content; (b) classifying the colon polyps as being malignant if the presence of at least one of (1)-(4) is determined and the presence of at least one of (5)-(15) is determined; and (c) classifying the colon polyps as not being malignant if the absence of each of (1)-(15) is determined. The mammal can be a human. The presence or absence of the increased level of the TERT polypeptide or mRNA encoding the TERT polypeptide can be determined. The presence or absence of the increased level of the FAP polypeptide or mRNA encoding the FAP polypeptide can be determined. The presence or absence of the increased level of the SOX11 polypeptide or mRNA encoding the SOX11 polypeptide can be determined. The presence or Attorney Docket No.07039-2155WO1 / 2022-250 absence of the increased level of the CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide can be determined. The method can include determining the presence of each of (1)-(4). The method can include determining the presence of each of (1)-(15). The method can include classifying the colon polyps as being malignant. The method can include determining the absence of each of (1)-(15). The method can include classifying the colon polyps as not being malignant. The sample can be a tissue sample including one or more polyp cells. In another aspect, this document features methods for assessing a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining (i) if a sample from a mammal having one or more colon polyps contains the presence or absence of at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, and (ii) if the sample contains the presence or absence of at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH; (b) classifying the colon polyps as being likely to recur if the presence of at least one of (1)-(5) is determined and at least one of (6)-(7) is determined; and (c) classifying the colon polyps as not being likely to recur if the absence of each of (1)-(7) is determined. The mammal can be a human. The presence or absence of the increased level of the TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide can be determined. The presence or absence of the increased level of the LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide can be determined. The presence or absence of the increased level of the DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide can be determined. The presence or absence of the increased level of the CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide can be determined. The presence or absence of the increased level of the DMKN polypeptide or mRNA encoding the DMKN polypeptide can be determined. The method can include determining the presence of each of (1)-(5). The method Attorney Docket No.07039-2155WO1 / 2022-250 can include determining the presence of each of (1)-(9). The method can include classifying the colon polyps as being likely to recur. The method can include determining the absence of each of (1)-(9). The method can include classifying the colon polyps as not being likely to recur. The sample can be a tissue sample including one or more polyp cells. The method also can include determining if the sample contains the presence or absence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. The method can include classifying the colon polyps as being likely to recur if the presence of the decreased level of the IGLL5 polypeptide or the decreased level of the mRNA encoding said IGLL5 polypeptide is determined. The method can include classifying the colon polyps as not being likely to recur if the absence of the decreased level of said IGLL5 polypeptide or the decreased level of the mRNA encoding said IGLL5 polypeptide is determined. In another aspect, this document features methods for selecting a treatment for a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining (i) that a sample from mammal having one or more colon polyps contains the presence of at least one of (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide, and (ii) that the sample contains the presence of at least one of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content, where the sample is a tissue sample including one or more polyp cells; and (b) selecting the mammal for surgery to remove the polyps and a cancer treatment. The mammal can be a Attorney Docket No.07039-2155WO1 / 2022-250 human. The surgery to remove the polyps can be a polypectomy. The cancer treatment can include radiation therapy. The cancer treatment can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, or any combination thereof. In another aspect, this document features methods for selecting a treatment for a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having one or more colon polyps contains the absence of (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, (4) an increased level of a CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide, (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content, where the sample is a tissue sample including one or more polyp cells; and (b) selecting the mammal for a colon polyp treatment in the absence of a cancer treatment. The mammal can be a human. The colon polyp treatment can be surgery to remove the polyps. The cancer treatment can include radiation therapy. The cancer treatment can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, or any combination thereof. In another aspect, this document features methods for selecting a treatment for a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining (i) that a sample from a mammal having one or more colon polyps Attorney Docket No.07039-2155WO1 / 2022-250 contains the presence of at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, and (ii) that the sample contains the presence of at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH, where the sample is a tissue sample including one or more polyp cells; and (b) selecting the mammal for colonoscopic polypectomy to remove the polyps. The mammal can be a human. The method also can include determining that the sample contains the presence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding the IGLL5 polypeptide. In another aspect, this document features methods for selecting a treatment for a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having one or more colon polyps contains the absence of (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH, where the sample is a tissue sample including one or more polyp cells; and (b) selecting the mammal for a colon polyp treatment, where the colon polyp treatment does not include any surgery to remove the polyps. The mammal can be a human. The method also can include determining that the sample from the mammal contains the absence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding the IGLL5 polypeptide. Attorney Docket No.07039-2155WO1 / 2022-250 In another aspect, this document features methods for treating a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining (i) that a sample from a mammal having one or more colon polyps includes one or more of (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide and (ii) that the sample includes one or more of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content; (b) subjecting the mammal to surgery to remove the polyps; and (c) administering a cancer treatment to the mammal. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The surgery to remove the polyps can be a polypectomy. The cancer treatment can include radiation therapy. The cancer treatment can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, or any combination thereof. The sample also can include a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding the IGLL5 polypeptide. In another aspect, this document features methods for treating colon polyps. The methods can include, or consist essentially of, subjecting a mammal identified as having a sample (i) including one or more of (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or Attorney Docket No.07039-2155WO1 / 2022-250 mRNA encoding the CXCL13 polypeptide, and (ii) including one or more of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content to a surgery to remove the polyps, and administering a cancer treatment to the mammal. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The surgery to remove the polyps can be a polypectomy. The cancer treatment can include radiation therapy. The cancer treatment can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, or any combination thereof. In another aspect, this document features methods for treating a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having one or more colon polyps lacks (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, (4) an increased level of a CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide, (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of NKC in the resting phase, (12) an increased frequency of genomic Attorney Docket No.07039-2155WO1 / 2022-250 DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content; and (b) administering a colon polyp treatment to the mammal in the absence of a cancer treatment. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The colon polyp treatment can be surgery to remove the polyps. The cancer treatment can include radiation therapy. The cancer treatment can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, or any combination thereof. In another aspect, this document features methods for treating colon polyps. The methods can include, or consist essentially of, subjecting a mammal identified as having a sample lacking (1) an increased level of a TERT polypeptide or mRNA encoding the TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding the FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding the SOX11 polypeptide, (4) an increased level of a CXCL13 polypeptide or mRNA encoding the CXCL13 polypeptide, (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding the ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding the THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding the SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding the CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding the SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding the VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content to a colon polyp treatment to the mammal in the absence of a cancer treatment. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The colon polyp treatment can be surgery to remove the polyps. The cancer treatment can include radiation therapy. The cancer treatment can include administering an anti-cancer drug to the mammal. The anti-cancer drug can be docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, or any combination thereof. Attorney Docket No.07039-2155WO1 / 2022-250 In another aspect, this document features methods for treating a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining (i) that a sample from a mammal having one or more colon polyps including at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, and (ii) that the sample including at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH; and (b) subjecting the mammal to colonoscopic polypectomy to remove the polyps. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The method also can include determining that the sample includes a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding the IGLL5 polypeptide. In another aspect, this document features methods for treating colon polyps. The methods can include, or consist essentially of, subjecting a mammal identified as having a sample (i) including at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, and (ii) including at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH to surgery to remove the polyps. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The method also can include determining the said sample contains a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. Attorney Docket No.07039-2155WO1 / 2022-250 In another aspect, this document features methods for treating a mammal having one or more colon polyps. The methods can include, or consist essentially of, (a) determining that a sample from a mammal having one or more colon polyps contains the absence of (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH, where the sample is a tissue sample including one or more polyp cells; and (b) selecting the mammal for a colon polyp treatment, where the colon polyp treatment does not include any surgery to remove the polyps. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The method also can include determining that said sample contains the absence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding the IGLL5 polypeptide. In another aspect, this document features methods for treating colon polyps. The methods can include, or consist essentially of, subjecting a mammal identified as having a sample lacking (1) an increased level of a TPRG1 polypeptide or mRNA encoding the TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding the LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding the DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding the CYP1A1 polypeptide, (5) an increased level of a DMKN polypeptide or mRNA encoding the DMKN polypeptide, (6) an increased level of a ZIC5 polypeptide or mRNA encoding the ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH to a colon polyp treatment, where the colon polyp treatment does not include any surgery to remove the polyps. The mammal can be a human. The sample can be a tissue sample including one or more polyp cells. The sample also can lack a Attorney Docket No.07039-2155WO1 / 2022-250 decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding the IGLL5 polypeptide. In another aspect, this document features methods performed by one or more computers, where the methods can include, or consist essentially of, (a) receiving a set of features characterizing a mammal having one or more colon polyps, and where the set of features comprises one or more transcriptomic features of the mammal; (b) processing the set of features characterizing the mammal using a polyp prediction machine learning model, in accordance with values of a set of machine learning model parameters, to generate a machine learning model output, where the machine learning model output defines one or more predictions characterizing the one or more colon polyps of the mammal; and generating a notification that indicates the one or more predictions characterizing the one or more colon polyps of the mammal. The machine learning model output can include a likelihood that the one or more colon polyps are malignant. The machine learning model output can include a likelihood that the one or more colon polyps will recur. The set of features characterizing the mammal can be derived from a sample obtained from the mammal. The set of features characterizing the mammal can include transcriptomic features. The transcriptomic features can include normalized values of one or more protein coding genes in the mammal. The transcriptomic features can include normalized values of one or more of: ADAMTS4 genes, THBS2 genes, SERPINE1 genes, FAP genes, CYR61 genes, SOX11 genes, CXCL13 genes, SFRP2 genes, VIP genes, or TERT genes. The set of features characterizing the mammal can include one or more of: genomic features, epigenomic features, proteomic features, or metabolomic features. The polyp prediction machine learning model can include one or more of: a linear regression model, a random forest model, a support vector machine model, a neural network model, or an XGBoost model. The polyp prediction machine learning model can have been trained by operations comprising: (a) obtaining a set of training examples, where each training example comprises: (i) a set of training features characterizing a training mammal having one or more colon polyps, and (ii) a target output characterizing the one or more colon polyps of the mammal; and (b) training the set of machine learning model parameters of the polyp prediction machine learning model on the set of training examples, comprising, for each training example: (i) training the polyp prediction machine learning model to process the set of training features from the training example to generate a machine Attorney Docket No.07039-2155WO1 / 2022-250 learning model output that matches the target output from the training example. The method can include taking an action based on the one or more predictions characterizing the one or more colon polyps of the mammal. The action can include increasing a rate of screening for the one or more colon polyps of the mammal. The action can include removing the one or more colon polyps of the mammal. The method can include generating a set of explainability data that explains the one or more predictions generated by the polyp prediction machine learning model, comprising: (a) generating, for each feature in the set of features characterizing the mammal, an impact score that characterizes an impact of the feature on the one or more predictions generated by the polyp prediction machine learning model for the one or more colon polyps of the mammal. The method can include: (a) identifying one or more features having the highest impact scores from among the set of features; and (b) generating a notification that indicates the one or more features having the highest impact scores from among the set of features. In another aspect, this document features systems comprising: (a) one or more computers; and (b) one or more storage devices communicatively coupled to the one or more computers, where the one or more storage devices store instructions that, when executed by the one or more computers, cause the one or more computers to perform operations of methods performed by one or more computers, where the methods can include, or consist essentially of, (a) receiving a set of features characterizing a mammal having one or more colon polyps, and where the set of features comprises one or more transcriptomic features of the mammal; (b) processing the set of features characterizing the mammal using a polyp prediction machine learning model, in accordance with values of a set of machine learning model parameters, to generate a machine learning model output, where the machine learning model output defines one or more predictions characterizing the one or more colon polyps of the mammal; and generating a notification that indicates the one or more predictions characterizing the one or more colon polyps of the mammal. In another aspect, this document features non-transitory computer storage media storing instructions that when executed by one or more computers cause the one or more computers to perform operations of methods performed by one or more computers, where the methods can include, or consist essentially of, (a) receiving a set of features characterizing a mammal having one or more colon polyps, and where the set of features comprises one or Attorney Docket No.07039-2155WO1 / 2022-250 more transcriptomic features of the mammal; (b) processing the set of features characterizing the mammal using a polyp prediction machine learning model, in accordance with values of a set of machine learning model parameters, to generate a machine learning model output, where the machine learning model output defines one or more predictions characterizing the one or more colon polyps of the mammal; and generating a notification that indicates the one or more predictions characterizing the one or more colon polyps of the mammal. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. DESCRIPTION OF THE DRAWINGS Figures 1A – 1G. Molecular features distinguish cancer adjacent polyps (CAPs) and cancer free polyps (CFPs) in a cohort (n=50 CAPs, n=50 CFPs) validating findings in a discovery set (n = 16 CFPs, n=15 CFPs). FIG.1A shows a schematic of the large intestine, with a cancer free polyp (CFP) and a cancer adjacent polyp (CAP) indicated. FIG.1B shows a pair of box-and-whisker plots of somatic mutation prevalence from whole-genome sequencing (WGS) data comparing CFPs and CAPs, for discovery (left) and validation (right) datasets, and also shows a pair of box-and-whisker plots of mean copy number variant (CNV) size (in basepairs) from whole-genome sequencing (WGS) data comparing CFPs and CAPs, for discovery (left) and validation (right) datasets. FIG.1C shows a volcano plot of differentially expressed genes between the CAP and CFP tissues as measured by RNA-seq. The x-axis is the log of the fold change in expression, and the y-axis is the log of the false discovery rate (FDR) between CAP and CFP tissues. Dots in the positive Log2 fold change to Attorney Docket No.07039-2155WO1 / 2022-250 the right of zero on the x-axis are genes that have a fold change???1, and FDR???0.05 (left), meaning upregulated in CAP compared to CFP. Dots in the negative Log2 fold change to the left of zero on the x-axis represent genes that are upregulated in CFPs. FIG.1D shows a pair of box-and-whisker plots of GREM1 gene expression for CFPs and CAPs, for discovery (left) and validation (right) sets. FIG.1E shows Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis for genes that are up-regulated in CAPs relative to CFPs. FIG.1F shows a pair of box-and-whisker plots of telomere content from WGS data for CFPs and CAP, for discovery (left) and validation (right) sets. FIG.1G shows a pair of box-and- whisker plots of normalized hTERT expression from RNA-seq for CFPs and CAPs, for discovery (left) and validation (right) sets. Figures 2A – 2D. Senescence-associated secretory phenotype (SASP), immune cell, and age-related analyses in polyps. FIG.2A shows a pair of box-and-whisker plots of senescence-associate secretory phenotype (SASP) gene expression between CAPs (left) and CFPs (right). FIG.2B shows a plot of gene set enrichment analysis (GSEA) of SASP expression in CAPs and in CFPs. FIG.2C shows a pair of box-and-whisker plots of population distributions between CAPs (left) and CFPs (right) for resting natural killer (NK) cells. FIG.2D shows a heatmap of gene expression data for early onset CAPs, early onset CFPs, and telomere length based on counts from RNA-seq data, showing the differentially expressed genes between CAPs and CFPs. Figures 3A – 3F. hTERT edited organoids compared to alterations between CAP and CFPs. FIG.3A shows a schematic for gene editing of organoids, using PiggyBac Transposon System comprising a vector + transposase = gene of interest (hTERT) insertion (left), which creates the TERT overexpressing (TERT⁺) organoids. Post-electroporation and puromycin selection with PiggyBac vector, showing edited organoids by brightfield microscopy (center) and GFP fluorescent microscopy (right). FIG.3B shows a plot of gene expression measured by qPCR on RNA extracted from organoids in the unedited organoids, HeLa cells, and TERT edited organoids. Fold change expression is plotted on y-axis relative to GAPDH. FIG.3C shows a table of normalized RNA-seq counts between TERT⁺ and unedited organoids for the TERT and GAPDH genes. FIG.3D shows a plot of GSEA comparing the differentially expressed genes between TERT⁺ and unedited organoids and CAP compared to CFP tissues (absolute value lfc > 0.1, pvalue < 0.05). For enrichment of TERT⁺ organoids compared to Attorney Docket No.07039-2155WO1 / 2022-250 genes with increased expression in CAPS, the Normalized Enrichment Score (NES) = 1.86, and Padj= 0.003. FIG.3E shows KEGG pathway analysis for the top 600 up-regulated genes in the TERT⁺ organoids. FIG.3F shows row scaled showing relative changes in SASP panel genes between TERT unedited and TERT⁺ organoids. Figures 4A – 4C. Model to predict CAPs from CFPs based on molecular features. FIG.4A shows a schematic of framework using AutoGluon for model creation and selection. FIG.4B shows a SHAP plot visualizing distribution of impacts each feature has on CAP vs CFP model output. FIG.4C shows features included in the model and resulting PPV and NPV value and the top DEGS (RNA/WGS = top DEGs (ADAMTS4, THBS2, SERPINE1, CYR61, SFRP2, FAP, VIP, SOX11, and CXCL13) distinguishing genetics features including deletions from CNV data; duplication from CNV data; loss of heterozygosity from CNV data; tel.cont = telomere content from Telomere Hunter analysis of WGS data and DEG in the resting natural killer cells. Figures 5A – 5GE. Molecular features to classify POP. FIG.5A shows a cartoon schematic of POP categories. including polyps that do not recur (POP-NR) and polyps that do recur (POP- R) at least one time compared to CAPs. FIG.5B shows a box-and-whisker plot of somatic mutation prevalence from WGS data for a (POP-NR) (left), POP-R (center), and CAP (right). FIG.5C shows a box-and-whisker plot of mean CNV event size from WGS data for POP-NA (left), POP-R (center), and CAP (right). All comparisons, “ns” indicates not significant a single asterisk indicates p < 0.05, and a double asterisk indicates p < 0.001. FIG.5D shows a volcano plot of differentially expressed genes for POP-NR compared to POP-R as measured by RNA-seq. The x-axis is the log of the fold change in expression, and the y-axis is the log of the FDR between POP-NR and POP-R tissues. Dots in the negative Log2 fold change to the left of zero on the x-axis are genes that have a fold change < -1, and FDR???0.05 in the POP-NR polyps meaning these genes are upregulated in the POP-NR compared to the POP-R tissues while dots in the positive Log2 fold change to the right of zero on the x-axis are genes that have a fold change???1 and FDR???0.05 in the POP-R, meaning these genes are upregulated in the POP-R compared to the POP-NR. FIG.5D also shows a volcano plot of differentially expressed genes for POP-NR compared to CAP as measured by RNA-seq. The x-axis is the log of the fold change in expression, and the y-axis is the log of the FDR between POP-NR and CAP tissues. Dots in the negative Log₂ fold Attorney Docket No.07039-2155WO1 / 2022-250 change to the left of zero on the x-axis are genes that have a fold change < -1, and FDR???0.05 in the POP-NR meaning these genes are upregulated in the POP-NR compared to the CAP tissues while dots in the positive Log2 fold change to the right of zero on the x-axis are genes that have a fold change???1 and FDR???0.05 in the CAP meaning these genes are upregulated in the CAP compared to the POP-NR. FIG.5D also shows a volcano plot of differentially expressed genes for POP-R compared to CAP as measured by RNA-seq. The x- axis is the log of the fold change in expression, and the y-axis is the log of the FDR between POP-R and CAP tissues. Dots in the negative Log₂ fold change to the left of zero on the x- axis are genes that have a fold change < -1, and FDR???0.05 in the POP-R polyps, meaning these genes are upregulated in the POP-R compared to the CAP while dots in the positive Log₂ fold change to the right of zero on the x-axis are genes that have a fold change???1 and FDR???0.05 in the CAP meaning these genes are upregulated in the CAP compared to the POP-R. FIG.5E shows a heatmap of data from KEGG Pathway Analysis for genes enriched between CAP and CFP, as well as by POP status. The right side of the heatmap shows each gene within the enriched pathways and corresponding somatic mutations as sample proportions across POP-NR, POP-R, and CAP that have a medium/high impact mutation for a particular gene. FIG.5F shows a box-and-whisker plot of telomere content from WGS data for POP-NR (left), POP-R (center), and CAP (right). All comparisons, “ns” indicates not significant, a single asterisk indicates p < 0.05, a double asterisk indicates p < 0.001, a triple asterisk indicates p < 0.0001 and a quadruple asterisk indicates p < 0.00001. FIG.5G shows a box-and-whisker plot of normalized hTERT expression from RNA-seq data for POP-NR (left), POP-R (center), CAP (right). All comparisons, “ns” indicates not significant, a single asterisk indicates p < 0.05, a double asterisk indicates p < 0.001, a triple asterisk indicates p < 0.0001 and a quadruple asterisk indicates p < 0.00001. Figures 6A – 6D. Polyp Recurrence based on KRAS mutation. FIG.6A shows KRAS mutation percentages within POPs. FIG.6B contains an expression panel showing comparisons of significant DEGs between POP-R KRAS mutant (n=20, left) to POP-R KRAS WT (n=11, right). FIG.6C contains an expression panel showing comparisons of significant DEGs between POP-R KRAS WT (n=11, left) to POP-NR (n=30, right). FIG.6D shows POP-NR vs POP-R linear regression model details. Attorney Docket No.07039-2155WO1 / 2022-250 Figures 7A – 7B. CIBERSORT signatures of (FIG.7A) resting CD4 memory cells and (FIG.7B) macrophages M0 are significantly upregulated in CAP polyps compared to CFP polyps. **: padj<0.01, ***: padj< 0.001. Figures 8A – 8B. Transposon based editing for hTERT. FIG.8A shows a Piggybac vector with hTERT inserted for gene editing. FIG.8B is a table showing copy number results using the Piggybac qPCR copy number kit (Catalog: PBC100A-1; System Bioscience). Last column indicates copy number for TERT+ organoids (Piggyback row), untransfected organoids, and water control. Figure 9. KEGG pathways enriched in DEGs that were downregulated in the TERT+ organoids. Figure 10. RNAscope. Results observed for the RNAscope assay for CFP (left) and CAP (right) polyp tissue from two patients not represented in the Discovery or Validation cohorts. In the RNAscope (20X), THBS2 mRNA is represented by dots of green signal (exemplar signal marked white arrowheads, CAP tissue only), with nuclei stained with DAPI. Figure 11. POP-R vs POP-NR bar plot of feature importance in linear regression model. Figure 12. Differentially expressed transcripts in epithelial and stromal compartments between POP categories for SSA-TSA polyps. Figure 13. Differentially expressed transcripts in epithelial and stromal compartments between POP categories for TA-TV-VA polyps. Figure 14. Polyp outcome phenotypes (POPs) representing index and subsequent polyp recurrences or transformation to cancer. D^ETAILED D^ESCRIPTION This document provides methods and materials for assessing and/or treating mammals (e.g., humans) having one or more polyps (e.g., one or more colon polyps). In some cases, this document provides methods and materials that can be used to determine whether or not one or more polyps (e.g., one or more colon polyps) within a mammal (e.g., a human) are or are likely to become malignant and/or are likely to recur (e.g., likely to recur in the same location from which the polyp was removed from the mammal). For example, a Attorney Docket No.07039-2155WO1 / 2022-250 sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the molecular profile of the polyp. As described herein, a distinct molecular profile can be present in a polyp that is or is likely to become malignant (e.g., as compared to a molecular profile that can be present in a benign polyp). This document also provides methods and materials for treating a mammal having one or more polyps (e.g., one or more colorectal polyps). For example, a treatment for a mammal having one or more polyps can be selected based, at least in part, on the molecular profile of the mammal’s polyp(s) as described herein. A mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed to determine whether the polyp(s) are or are likely to become malignant and/or are likely to recur by detecting the molecular profile of the polyp(s). In some cases, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps) can be assessed to determine if the polyp(s) are or are likely to become malignant and/or are likely to recur based, at least in part, on the molecular profile of the polyp(s). For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of altered levels (e.g., increased levels or decreased levels) of one or more (e.g., one, two, three, four, five, or more) of an ADAMTS4 polypeptide (or mRNA encoding a ADAMTS4 polypeptide), a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), a FAP polypeptide (or mRNA encoding a FAP polypeptide), a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), a VIP polypeptide (or mRNA encoding a VIP polypeptide), and a TERT polypeptide (or mRNA encoding a TERT polypeptide) to determine whether the polyp(s) are malignant. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for (a) the presence or absence of altered levels (e.g., increased levels or decreased levels) of one or more of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an LY6G6C polypeptide (or mRNA Attorney Docket No.07039-2155WO1 / 2022-250 encoding an LY6G6C polypeptide), a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), a CYP1A1polypeptide (or mRNA encoding a CYP1A1 polypeptide), a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), and/or (b) the presence or absence of one or more mutations in a KRAS polypeptide (or in a nucleic acid encoding a KRAS polypeptide), an increased frequency of genomic DELs, and/or an increased frequency of LOH, to determine whether the polyp(s) are likely to recur. Any type of mammal can be assessed and/or treated as described herein. Examples of mammals that can be assessed and/or treated as described herein include, without limitation, humans, non-human primates (e.g., monkeys), dogs, cats, horses, cows, pigs, sheep, rabbits, mice, and rats. In some cases, the mammal can be a human. In some cases, the mammal can be a mammal having one or more polyps. In some cases, the mammal can have one or more polyp disorders (e.g., one or more hereditary polyp disorders). Examples of hereditary polyp disorders can include, without limitation, Lynch syndrome, familial adenomatous polyposis (FAP), Gardner’s syndrome, MYH-associated polyposis (MAP), Peutz-Jeghers syndrome, serrated polyposis syndrome and juvenile polyposis syndrome (JPS). For example, a mammal having one or more polyps can be assessed for whether a polyp is or is likely to become malignant and/or may be likely to recur, and can be treated with one or more interventions as described herein. A mammal (e.g., a human) having one or more polyps can have any type of polyp(s). In some cases, a polyp can be a non-neoplastic polyp (e.g., hyperplastic polyps, inflammatory polyps, and hamartomatous polyps). In some cases, a polyp can be a neoplastic polyp (e.g., adenomas and serrated polyps). A mammal (e.g., a human) having one or more polyps can have polyp(s) in any location within the mammal. Examples of locations within a mammal that can have one or more polyps that can be assessed and/or treated as described herein can include, without limitation, the colon and the rectum. In some cases, a polyp that is assessed and/or treated using the methods and materials described herein can be a colon polyp. In some cases, a polyp that is assessed and/or treated using the methods and materials described herein can be Attorney Docket No.07039-2155WO1 / 2022-250 a colon polyp. In some cases, a polyp that is assessed and/or treated using the methods and materials described herein can be a colorectal polyp. A mammal (e.g., a human) having one or more polyps can have any size polyp(s). In some cases, a polyp can be from about 0.5 mm to about 60 mm in size (e.g., across its diameter or longest dimension). For example, a polyp can be from about 0.5 mm to about 50 mm, from about 0.5 mm to about 40 mm, from about 0.5 mm to about 30 mm, from about 0.5 mm to about 20 mm, from about 0.5 mm to about 10 mm, from about 0.5 mm to about 5 mm, from about 1 mm to about 60 mm, from about 5 mm to about 60 mm, from about 10 mm to about 60 mm, from about 20 mm to about 60 mm, from about 30 mm to about 60 mm, from about 40 mm to about 60 mm, from about 50 mm to about 60 mm, from about 1 mm to about 50 mm, from about 10 mm to about 40 mm, from about 20 mm to about 30 mm¸ from about 10 mm to about 30 mm, from about 20 mm to about 40 mm, from about 30 mm to about 50 mm, from about 1 mm to about 10 mm, from about 10 mm to about 20 mm, from about 20 mm to about 30 mm, from about 30 mm to about 40 mm, or from about 40 mm to about 50 mm in size. A mammal (e.g., a human) having one or more polyps can have any number of polyps. In some cases, a mammal can have from about one polyp to about 1000 polyps. For example, a mammal can have from about 1 to about 750, from about 1 to about 500, from about 1 to about 250, from about 1 to about 100, from about 1 to about 50, from about 100 to about 1000, from about 250 to about 1000, from about 500 to about 1000, from about 750 to about 1000, from about 100 to about 750, from about 200 to about 500, from about 50 to about 100¸ from about 100 to about 250, from about 250 to about 500, or from about 500 to about 1000 polyps. In some cases, a mammal can have two or more polyps (e.g., two three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more polyps). In some cases, a mammal (e.g., a human) that is assessed and/or treated as described herein can be identified as having one or more polyps. Any appropriate method can be used to identify a mammal as having one or more polyps. In some cases, imaging techniques such as using a flexible tube with a light and camera attached to it to visualize internal organs (e.g., colonoscopy such as video capsule colonoscopy and sigmoidoscopy) and computerized tomography (CT) scanning (e.g., CT colonography), can be used to identify a mammal as having one or more polyps. In some cases, laboratory tests such as stool-based tests (e.g., Attorney Docket No.07039-2155WO1 / 2022-250 checking for the presence of blood in the stool and/or assessing DNA within stool) can be used to identify a mammal as having one or more polyps. In some cases, physical examinations (e.g., digital rectal examinations) can be used to identify a mammal as having one or more polyps. Any appropriate sample from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed as described herein. In some cases, a sample can be a biological sample. For example, a sample can be a polyp sample (e.g., can contain one or more polyp cells). In some cases, a polyp sample can contain one or more polyp cells from a single polyp. In some cases, a polyp sample can contain one or more polyp cells from more than one polyp (e.g., from two, three, four, five, or more polyps). In some cases, a sample can contain one or more biological molecules (e.g., nucleic acids such as DNA and RNA, proteins, carbohydrates, lipids, hormones, metabolites, and/or microbiota). Examples of samples that can be assessed as described herein include, without limitation, tissue samples (e.g., colon tissue samples and rectum tissue samples), stool samples, cellular samples (e.g., buccal samples and skin samples), fluid samples (e.g., blood, serum, plasma, urine, saliva, and sweat), and expired (exhaled) breath samples. A biological sample can be a fresh sample or a fixed sample. In some cases, a biological sample can be a processed sample (e.g., an embedded sample such as a paraffin or OCT embedded sample). In some cases, a sample can be processed to isolate or extract one or more biological molecules. For example, a colon tissue sample and/or a rectal tissue sample can be obtained from a mammal having one or more polyps and can be assessed to determine if a polyp within the mammal is or is likely to become malignant and/or is likely to recur based, at least in part, on a molecular profile of the polyp. A molecular profile described herein can include any appropriate number of biomarkers. In some cases, a molecular profile described herein can include a panel of biomarkers. A panel of biomarkers can include any number of biomarkers. For example, a panel of biomarkers can include any two or more (e.g., two, three, four, five, six, seven, or more) biomarkers. In some cases, a biomarker can include the presence, absence, or level of a polypeptide (or an mRNA encoding a polypeptide). In some cases, a biomarker can include the presence or absence or one or more mutations within a polypeptide (or a nucleic acid encoding a polypeptide). In some cases, a biomarker can include a somatic mutation Attorney Docket No.07039-2155WO1 / 2022-250 prevalence. In some cases, a biomarker can include an amount of copy number variation (CNVs). In some cases, a biomarker can be a chromosomal rearrangement. Examples of types of chromosomal rearrangements include, without limitation, genomic insertions, genomic insertion/deletions (INDELs), genomic DUPs, genomic DELs (e.g., a genomic DEL resulting in LOH). In some cases, a biomarker can be a change in telomere structure (e.g., telomere content and telomere length). In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides). A polypeptide that can have an altered level in a polyp that is or is likely to become malignant and/or is likely to recur can be involved in a cellular pathway such as a protein digestion and absorption pathway, a viral infection pathway, a focal adhesion pathway, a PI3K-Akt pathway, a transcriptional misregulation pathway (e.g., a cancer-related transcriptional misregulation pathway), and a senescence-associated secretory phenotype (SASP)-associated pathway. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides) to determine whether or not the polyp(s) are malignant. In some cases, a polyp within a mammal having one or more polyps (e.g., one or more colon polyps) can be identified as being or likely to become malignant based, at least in part, on a molecular profile that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a sample containing one or more polyp cells) obtained from the mammal. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of an altered level (e.g., an increased level or a decreased level) of one or more polypeptides (or mRNA encoding such polypeptides) to determine whether or not the polyp(s) are likely to recur. In some cases, a polyp within a mammal having one or more polyps (e.g., one or more colon polyps) can be identified as being likely to recur based, at least in part, on a molecular profile Attorney Docket No.07039-2155WO1 / 2022-250 that includes the presence of an altered level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a sample containing one or more polyp cells) obtained from the mammal. In some cases, an altered level can be an increased level of one or more polypeptides (or mRNA encoding such polypeptides) in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). The term “increased level” as used herein with respect to a level of a polypeptide (or mRNA encoding that polypeptide) in a sample refers to any level that is higher than a reference level of the polypeptide (or mRNA). In some cases, an altered level can be a decreased level of a polypeptide (or mRNA encoding that polypeptide) in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps). The term “decreased level” as used herein with respect to a level of a polypeptide (or mRNA encoding that polypeptide) in a sample refers to any level that is lower than a reference level of the polypeptide (or mRNA). The term “reference level” as used herein with respect to a level of a polypeptide (or mRNA) refers to the level of the polypeptide (or mRNA) typically observed in a control sample. Examples of control samples include, without limitation, samples obtained from mammals having no polys (e.g., samples from healthy mammals and matched normal samples from mammals having one or more polyps), and samples from mammals having one or more polyps (e.g., one or more colon polyps) that did not progress to cancer, and samples obtained from mammals having one or more polyps (e.g., one or more colon polyps) that did not recur. It will be appreciated that levels of polypeptides (or mRNAs) from comparable samples are used when determining whether or not a particular level is an altered level of a polypeptide (or mRNA). In some cases, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence, absence, or level of any appropriate polypeptides (or mRNAs encoding the polypeptides). Examples of polypeptides that can be present at an altered level in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps) and where the polyp(s) are or are likely to become malignant and/or are likely recur include, without limitation, an ADAMTS4 polypeptide, a THBS2 polypeptide, a SERPINE1 polypeptide, a FAP Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide (or mRNA encoding a FAP polypeptide), a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), a SFRP2 polypeptide, a VIP polypeptide, a TERT polypeptide, a TPRG1 polypeptide, an IGLV3-12 polypeptide, an LY6G6C polypeptide, a DUSP4 polypeptide, a ZIC5 polypeptide, a CYP1A1 polypeptide, a DMKN polypeptide, and an IGLL5 polypeptide. Examples of mRNAs that can be present at an altered level in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps) and where the polyp(s) are or are likely to become malignant and/or are likely recur include, without limitation, mRNAs encoding an ADAMTS4 polypeptide, a THBS2 polypeptide, a SERPINE1 polypeptide, a FAP polypeptide, a CYR61 polypeptide, a SOX11 polypeptide, a CXCL13 polypeptide, a SFRP2 polypeptide, a VIP polypeptide, a TERT polypeptide, a TPRG1 polypeptide, an IGLV3-12 polypeptide, an LY6G6C polypeptide, a DUSP4, a ZIC5 polypeptide, a CYP1A1 polypeptide, a DMKN polypeptide, and an IGLL5 polypeptide. In some cases, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence, absence, or level of one or more of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), a FAP polypeptide (or mRNA encoding a FAP polypeptide), a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), a VIP polypeptide (or mRNA encoding a VIP polypeptide), and a TERT polypeptide (or mRNA encoding a TERT polypeptide). In some cases, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence, absence, or level of one or more of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), a DMKN polypeptide (or mRNA encoding a Attorney Docket No.07039-2155WO1 / 2022-250 DMKN polypeptide), and an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide). In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide). Examples of ADAMTS4 polypeptides and nucleic acid sequences encoding an ADAMTS4 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENST00000367996, ENST00000478394, and ENST00000367995. For example, an altered level of an ADAMTS4 polypeptide (or an mRNA encoding an ADAMTS4 polypeptide) can be any level that is higher or lower than a reference level of the ADAMTS4 polypeptide (or a reference level of an mRNA encoding an ADAMTS4 polypeptide). In some case, a reference level of an ADAMTS4 polypeptide in humans can be a level of an ADAMTS4 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 picograms (pg) of ADAMTS4 polypeptide per polyp cell. For example, an increased level of an ADAMTS4 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of an ADAMTS4 polypeptide. For example, an increased level of an ADAMTS4 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of an ADAMTS4 polypeptide. For example, a decreased level of an ADAMTS4 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of an ADAMTS4 polypeptide. For example, a decreased level of an ADAMTS4 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of an ADAMTS4 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide). Examples of THBS2 polypeptides and nucleic acid sequences encoding a THBS2 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. Attorney Docket No.07039-2155WO1 / 2022-250 ENST00000366787 and ENST00000617924. For example, an altered level of a THBS2 polypeptide (or an mRNA encoding a THBS2 polypeptide) can be any level that is higher or lower than a reference level of the THBS2 polypeptide (or a reference level of an mRNA encoding a THBS2 polypeptide). In some case, a reference level of a THBS2 polypeptide in humans can be a level of a THBS2 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of THBS2 polypeptide per polyp cell. For example, an increased level of a THBS2 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a THBS2 polypeptide. For example, an increased level of a THBS2 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a THBS2 polypeptide. For example, a decreased level of a THBS2 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a THBS2 polypeptide. For example, a decreased level of a THBS2 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a THBS2 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide). Examples of SERPINE1 polypeptides and nucleic acid sequences encoding a SERPINE1 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID No. ENST00000223095. For example, an altered level of a SERPINE1 polypeptide (or an mRNA encoding a SERPINE1 polypeptide) can be any level that is higher or lower than a reference level of the SERPINE1 polypeptide (or a reference level of an mRNA encoding a SERPINE1 polypeptide). In some case, a reference level of a SERPINE1 polypeptide in humans can be a level of a SERPINE1 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of SERPINE1 polypeptide per polyp cell. For example, an increased level of a SERPINE1 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a SERPINE1 polypeptide. For example, an Attorney Docket No.07039-2155WO1 / 2022-250 increased level of a SERPINE1 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a SERPINE1 polypeptide. For example, a decreased level of a SERPINE1 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a SERPINE1 polypeptide. For example, a decreased level of a SERPINE1 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a SERPINE1 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a FAP polypeptide (or mRNA encoding a FAP polypeptide). Examples of FAP polypeptides and nucleic acid sequences encoding a FAP polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensemble ID Nos. ENST00000422436, ENST00000480044, and ENST00000188790. For example, an altered level of a FAP polypeptide (or an mRNA encoding a FAP polypeptide) can be any level that is higher or lower than a reference level of the FAP polypeptide (or a reference level of an mRNA encoding a FAP polypeptide). In some case, a reference level of a FAP polypeptide in humans can be a level of a FAP polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of FAP polypeptide per polyp cell. For example, an increased level of a FAP polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a FAP polypeptide. For example, an increased level of a FAP polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a FAP polypeptide. For example, a decreased level of a FAP polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a FAP polypeptide. For example, a decreased level of a FAP polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a FAP polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level Attorney Docket No.07039-2155WO1 / 2022-250 of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide). Examples of CYR61 polypeptides and nucleic acid sequences encoding a CYR61 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENST00000451137, and ENST00000480413. For example, an altered level of a CYR61 polypeptide (or an mRNA encoding a CYR61 polypeptide) can be any level that is higher or lower than a reference level of the CYR61 polypeptide (or a reference level of an mRNA encoding a CYR61 polypeptide). In some case, a reference level of a CYR61 polypeptide in humans can be a level of a CYR61 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of CYR61 polypeptide per polyp cell. For example, an increased level of a CYR61 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a CYR61 polypeptide. For example, an increased level of a CYR61 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a CYR61 polypeptide. For example, a decreased level of a CYR61 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a CYR61 polypeptide. For example, a decreased level of a CYR61 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a CYR61 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide). Examples of SOX11 polypeptides and nucleic acid sequences encoding a SOX11 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensemble ID No. ENST00000322002. For example, an altered level of a SOX11 polypeptide (or an mRNA encoding a SOX11 polypeptide) can be any level that is higher or lower than a reference level of the SOX11 polypeptide (or a reference level of an mRNA encoding a SOX11 polypeptide). In some case, a reference level of a SOX11 polypeptide in humans can be a level of a SOX11 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of SOX11 polypeptide per polyp cell. For example, Attorney Docket No.07039-2155WO1 / 2022-250 an increased level of a SOX11 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a SOX11 polypeptide. For example, an increased level of a SOX11 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a SOX11 polypeptide. For example, a decreased level of a SOX11 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a SOX11 polypeptide. For example, an increased level of a SOX11 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a SOX11 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a CXCL13 polypeptide (or an increased level of an mRNA encoding a CXCL13 polypeptide). Examples of CXCL13 polypeptides and nucleic acid sequences encoding a CXCL13 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensemble ID Nos ENSG00000156234, ENST00000286758, and ENST00000506590. For example, an altered level of a CXCL13 polypeptide (or an mRNA encoding a CXCL13 polypeptide) can be any level that is higher or lower than a reference level of the CXCL13 polypeptide (or a reference level of an mRNA encoding a CXCL13 polypeptide). In some case, a reference level of a CXCL13 polypeptide in humans can be a level of a CXCL13 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of CXCL13 polypeptide per polyp cell. For example, an increased level of a CXCL13 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a CXCL13 polypeptide. For example, an increased level of a CXCL13 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a CXCL13 polypeptide. For example, a decreased level of a CXCL13 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a CXCL13 polypeptide. For example, a decreased level of a CXCL13 polypeptide can be a level that is Attorney Docket No.07039-2155WO1 / 2022-250 at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a CXCL13 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide). Examples of SFRP2 polypeptides and nucleic acid sequences encoding a SFRP2 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID No. ENST00000274063. For example, an altered level of a SFRP2 polypeptide (or an mRNA encoding a SFRP2 polypeptide) can be any level that is higher or lower than a reference level of the SFRP2 polypeptide (or a reference level of an mRNA encoding a SFRP2 polypeptide). In some case, a reference level of a SFRP2 polypeptide in humans can be a level of a SFRP2 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of SFRP2 polypeptide per polyp cell. For example, an increased level of a SFRP2 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a SFRP2 polypeptide. For example, an increased level of a SFRP2 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a SFRP2 polypeptide. For example, a decreased level of a SFRP2 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a SFRP2 polypeptide. For example, a decreased level of a SFRP2 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a SFRP2 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include altered level of a VIP polypeptide (or mRNA encoding a VIP polypeptide). Examples of VIP polypeptides and nucleic acid sequences encoding a VIP polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensemble ID Nos. ENST00000367243, ENST00000431366, and ENST00000431366. For example, an altered level of a VIP polypeptide (or an mRNA encoding a VIP polypeptide) can be any level that is Attorney Docket No.07039-2155WO1 / 2022-250 higher or lower than a reference level of the VIP polypeptide (or a reference level of an mRNA encoding a VIP polypeptide). In some case, a reference level of a VIP polypeptide in humans can be a level of a VIP polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of VIP polypeptide per polyp cell. For example, an increased level of a VIP polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a VIP polypeptide. For example, an increased level of a VIP polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a VIP polypeptide. For example, a decreased level of a VIP polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a VIP polypeptide. For example, a decreased level of a VIP polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a VIP polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a TERT polypeptide (or mRNA encoding a TERT polypeptide). Examples of TERT polypeptides and nucleic acid sequences encoding a TERT polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENSG00000164362, ENST00000310581, ENST00000508104, ENST00000484238, and ENST00000310581. For example, an altered level of a TERT polypeptide (or an mRNA encoding a TERT polypeptide) can be any level that is higher or lower than a reference level of the TERT polypeptide (or a reference level of an mRNA encoding a TERT polypeptide). In some case, a reference level of a TERT polypeptide in humans can be a level of a TERT polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of TERT polypeptide per polyp cell. For example, an increased level of a TERT polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a TERT polypeptide. For example, an increased level of a TERT polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a TERT polypeptide. For example, a decreased level of a TERT polypeptide can be at least Attorney Docket No.07039-2155WO1 / 2022-250 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a TERT polypeptide. For example, a decreased level of a TERT polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a TERT polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide). Examples of TPRG1 polypeptides and nucleic acid sequences encoding a TPRG1 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENST00000433971, ENST00000496671, and ENST00000345063. For example, an altered level of a TPRG1 polypeptide (or an mRNA encoding a TPRG1 polypeptide) can be any level that is higher or lower than a reference level of the TPRG1 polypeptide (or a reference level of an mRNA encoding a TPRG1 polypeptide). In some case, a reference level of a TPRG1 polypeptide in humans can be a level of a TPRG1 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of TPRG1 polypeptide per polyp cell. For example, an increased level of a TPRG1 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a TPRG1 polypeptide. For example, an increased level of a TPRG1 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a TPRG1 polypeptide. For example, a decreased level of a TPRG1 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a TPRG1 polypeptide. For example, a decreased level of a TPRG1 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a TPRG1 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide). Examples of LY6G6C polypeptides and nucleic acid sequences encoding an LY6G6C polypeptide include, Attorney Docket No.07039-2155WO1 / 2022-250 without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENST00000495859 and ENST00000375819. For example, an altered level of an LY6G6C polypeptide (or an mRNA encoding an LY6G6C polypeptide) can be any level that is higher or lower than a reference level of the LY6G6C polypeptide (or a reference level of an mRNA encoding an LY6G6C polypeptide). In some case, a reference level of an LY6G6C polypeptide in humans can be a level of an LY6G6C polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of LY6G6C polypeptide per polyp cell. For example, an increased level of an LY6G6C polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of an LY6G6C polypeptide. For example, an increased level of an LY6G6C polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of an LY6G6C polypeptide. For example, a decreased level of an LY6G6C polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of an LY6G6C polypeptide. For example, a decreased level of an LY6G6C polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of an LY6G6C polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide). Examples of DUSP4 polypeptides and nucleic acid sequences encoding a DUSP4 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensemble ID Nos. ENST00000240100 and ENST00000240101. For example, an altered level of a DUSP4 polypeptide (or an mRNA encoding a DUSP4 polypeptide) can be any level that is higher or lower than a reference level of the DUSP4 polypeptide (or a reference level of an mRNA encoding a DUSP4 polypeptide). In some case, a reference level of a DUSP4 polypeptide in humans can be a level of a DUSP4 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of DUSP4 polypeptide per polyp cell. For example, an increased level of a DUSP4 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a Attorney Docket No.07039-2155WO1 / 2022-250 reference level of a DUSP4 polypeptide. For example, an increased level of a DUSP4 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a DUSP4 polypeptide. For example, a decreased level of a DUSP4 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a DUSP4 polypeptide. For example, a decreased level of a DUSP4 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a DUSP4 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide). Examples of ZIC5 polypeptides and nucleic acid sequences encoding a ZIC5 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID No. ENST00000267294. For example, an altered level of a ZIC5 polypeptide (or an mRNA encoding a ZIC5 polypeptide) can be any level that is higher or lower than a reference level of the ZIC5 polypeptide (or a reference level of an mRNA encoding a ZIC5 polypeptide). In some case, a reference level of a ZIC5 polypeptide in humans can be a level of a ZIC5 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of ZIC5 polypeptide per polyp cell. For example, an increased level of a ZIC5 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a ZIC5 polypeptide. For example, an increased level of a ZIC5 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a ZIC5 polypeptide. For example, a decreased level of a ZIC5 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a ZIC5 polypeptide. For example, a decreased level of a ZIC5 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a ZIC5 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein Attorney Docket No.07039-2155WO1 / 2022-250 (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide). Examples of CYP1A1 polypeptides and nucleic acid sequences encoding a CYP1A1 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENST00000379727, ENST00000567032, and ENST00000395048. For example, an altered level of a CYP1A1 polypeptide (or an mRNA encoding a CYP1A1 polypeptide) can be any level that is higher or lower than a reference level of the CYP1A1 polypeptide (or a reference level of an mRNA encoding a CYP1A1 polypeptide). In some case, a reference level of a CYP1A1 polypeptide in humans can be a level of a CYP1A1 polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of CYP1A1 polypeptide per polyp cell. For example, an increased level of a CYP1A1 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a CYP1A1 polypeptide. For example, an increased level of a CYP1A1 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a CYP1A1 polypeptide. For example, a decreased level of a CYP1A1 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a CYP1A1 polypeptide. For example, a decreased level of a CYP1A1 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a CYP1A1 polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide). Examples of DMKN polypeptides and nucleic acid sequences encoding a DMKN polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID No. ENST00000489395. For example, an altered level of a DMKN polypeptide (or an mRNA encoding a DMKN polypeptide) can be any level that is higher or lower than a reference level of the DMKN polypeptide (or a reference level of an mRNA encoding a DMKN polypeptide). In some case, a reference level of a DMKN polypeptide in humans can be a Attorney Docket No.07039-2155WO1 / 2022-250 level of a DMKN polypeptide in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of 0.00061 pg of DMKN polypeptide per polyp cell. For example, an increased level of a DMKN polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of a DMKN polypeptide. For example, an increased level of a DMKN polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold greater than a reference level of a DMKN polypeptide. For example, a decreased level of a DMKN polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of a DMKN polypeptide. For example, a decreased level of a DMKN polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of a DMKN polypeptide. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an altered level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide). Examples of IGLL5 polypeptides and nucleic acid sequences encoding an IGLL5 polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID No. ENSG00000254709. For example, a decreased level of an IGLL5 polypeptide can be at least 50% (e.g., about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) lower than a reference level of an IGLL5 polypeptide. For example, a decreased level of an IGLL5 polypeptide can be a level that is at least 0.5 (e.g., at least 1, at least 2, at least 3, at least 4, or at least 5) fold less than a reference level of an IGLL5 polypeptide. Any appropriate method can be used to determine the presence, absence, or level of a polypeptide or mRNA encoding that polypeptide. In some cases, the presence, absence, or level of a polypeptide can be assessed by detecting and/or quantifying the polypeptide. Examples of methods that can be used to detect and/or quantify polypeptides include, without limitation, immunohistochemistry (IHC) techniques, mass spectrometry techniques (e.g., proteomics-based mass spectrometry assays or targeted quantification-based mass spectrometry assays), and western blotting techniques. In some cases, the presence, absence, or level of an mRNA encoding a polypeptide can be assessed by detecting and/or quantifying Attorney Docket No.07039-2155WO1 / 2022-250 the mRNA encoding a polypeptide. Examples of methods that can be used to detect and/or quantify mRNA include, without limitation, RT-PCR techniques (e.g., quantitative RT-PCR techniques), and next-generation sequencing (NGS) techniques (e.g., RNA sequencing (RNA-Seq) techniques). In some cases, the presence, absence, or level of a polypeptide and/or mRNA encoding that polypeptide can be identified as described in Example 1. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include one or more mutated polypeptides. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of one or more mutations in one or more polypeptides. The term “mutation” as used herein with respect to a polypeptide refers to a modification in the amino acid sequence as compared to a wild type amino acid for a particular species. A mutation can be any type of mutation including, without limitation, an insertion of one or more amino acids, a deletion of one or more amino acids, a substitution of one or more amino acids, and combinations thereof. In some cases, a mutation in a polypeptide can cause altered polypeptide activity. A polyp that is or is likely to become malignant and/or is likely to recur can have the presence of one or more mutations in any appropriate one or more polypeptides in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). In some cases, a KRAS polypeptide within a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of one or more mutations. Examples of wild type KRAS polypeptides and nucleic acid sequences encoding a KRAS polypeptide include, without limitation, those set forth in the Ensembl genome browser at, for example, Ensembl ID Nos. ENST00000311936, ENSG00000133703, and ENST00000556131. In some cases, a mutation that can be present in a KRAS polypeptide included in a molecular profile that can be used to identify a mammal (e.g., a human) as having one or more polyps (e.g., one or more colon polyps) that are or are likely to become malignant and/or are likely to recur can be as described in Example 4. Attorney Docket No.07039-2155WO1 / 2022-250 Any appropriate method can be used to detect the presence or absence of one or more mutations in a polypeptide within a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). For example, mass spectrometry, Edman degradation, and NGS techniques can be used to identify the presence or absence of one or more mutations in a polypeptide (e.g., a KRAS polypeptide). In some cases, nucleic acid encoding a polypeptide (e.g., nucleic acid encoding a KRAS polypeptide) such as DNA or RNA can be assessed to detect the presence or absence of one or more mutations in that polypeptide within a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). For example, nucleic acid sequencing techniques can be used to detect the presence or absence of one or more mutations in a polypeptide (e.g., a KRAS polypeptide). In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an elevated somatic mutation prevalence. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of an elevated somatic mutation prevalence. The term “elevated” as used herein with respect to a somatic mutation prevalence in a sample refers to any level that is higher than a reference level of somatic mutation prevalence. For example, an elevated somatic mutation prevalence can be at least 5% (e.g., about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of somatic mutation prevalence. For example, an elevated somatic mutation prevalence can be a prevalence that is at least 2 (e.g., at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of somatic mutation prevalence. Any appropriate method can be used to determine the somatic mutation prevalence of a polyp. In some cases, whole genome sequence, RNAseq, and/or gene panel tests can be used to determine a somatic mutation prevalence. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein Attorney Docket No.07039-2155WO1 / 2022-250 (e.g., based, at least in part, on the molecular profile of the polyp) can include an elevated copy number variation (e.g., an elevated mean copy number variation). For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of an elevated copy number variation. In some cases, an elevated copy number variation (e.g., a mean copy number variation) can include a larger size repeated region (e.g., an elevated copy number variation size). The term “elevated” as used herein with respect to a copy number variation size in a sample refers to any level that is higher than a reference level of copy number variation size. In some case, a reference level of copy number variation size in humans can be a copy number variation size in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of about 80000 base pairs. For example, an elevated copy number variation size can be at least 5% (e.g., about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of copy number variation size. For example, an elevated copy number variation size can be a variation that is at least 2 (e.g., at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of copy number variation size. Any appropriate method can be used to determine the copy number variation of a polyp. In some cases, RNAseq, fluorescent in situ hybridization, and/or comparative genomic hybridization can be used to determine a copy number variation. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include one or more chromosomal rearrangements (e.g., genomic insertions, genomic INDELs, genomic DUPs, and genomic DELs such as genomic DELs resulting in LOH). For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of one or more chromosomal rearrangements. The term “chromosomal rearrangement” as used herein refers to a chromosome abnormality involving a change in the structure of the native chromosome for a particular species. A chromosomal rearrangement can be any type of chromosomal rearrangement including, without limitation, genomic Attorney Docket No.07039-2155WO1 / 2022-250 insertions, genomic INDELs, genomic DUPs, and genomic DELs, and combinations thereof. In some cases, a chromosomal rearrangement can result in LOH. A polyp that is or is likely to become malignant and/or is likely to recur can have the presence of one or more chromosomal rearrangements in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). Any appropriate method can be used to determine the presence or absence of a chromosomal rearrangement within a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). In some cases, comparative genomic hybridization, CNV panel testing, and/or whole genome sequencing can be used to detect a chromosomal rearrangement. In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include one or more changes in telomere structure (e.g., telomere content and telomere length). For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of telomere structure (e.g., telomere content and telomere length). In some cases, a change in telomere structure can be an increase in telomere content (e.g., an increase in the number of TTAGG repeats present in a telomere). In some cases, a change in telomere structure can be an increase in telomere length. A polyp that is or is likely to become malignant and/or is likely to recur can have the presence of one or more chromosomal rearrangements in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). Any appropriate method can be used to determine the presence or absence of a change in telomere structure (e.g., telomere content and telomere length) within a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). In some cases, TelomereHunter software, mmqPCR, TeloFISH, and/or Southern blotting can be used to detect a change in telomere structure. Attorney Docket No.07039-2155WO1 / 2022-250 In some cases, a molecular profile used to determine whether or not a polyp (e.g., a colon polyp) is or is likely to become malignant and/or is likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyp) can include an increased number of NKCs in the resting phase. For example, a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be assessed for the presence or absence of an increased number of NKCs in the resting phase. The term “increased” as used herein with respect to a number of NKCs in the resting phase in a sample refers to any level that is higher than a reference level of NKCs in the resting phase. In some case, a reference level of NKCs in the resting phase in humans can be a number of NKCs in the resting phase in a sample (e.g., a sample containing one or more polyp cells) obtained from the human of about 1000 cells/mL sample. For example, an increased number of NKCs in the resting phase can be at least 5% (e.g., about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of NKCs in the resting phase. For example, an increased number of NKCs in the resting phase can be at least 2 (e.g., at least 5, at least 10, at least 15, at least 20, at least 25, at least 35, or at least 50) fold greater than a reference level of NKCs in the resting phase. Any appropriate method can be used to determine the number of NKCs in the resting phase within a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). In some cases, CIBERSORT and/or immunoFISH can be used to determine the number of NKCs in the resting phase. In some cases, the molecular profile of a polyp can be used to identify the polyp as being or likely to become malignant. For example, the presence of one or more of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and one or more changes in telomere structure (e.g., telomere content and telomere length) in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be used to identify the polyp(s) as being or likely to become malignant. In some cases, the molecular profile of a polyp can be used to identify the polyp as not being or not likely to become malignant. For example, the absence of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length) in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be used to identify the polyp(s) as not being or not likely to become malignant. In some cases, when a polyp is assessed to determine whether or not the polyp is malignant as described herein (e.g., based, at least in part, on the molecular profile of the polyp), the determination can be confirmed using one or more additional diagnostic Attorney Docket No.07039-2155WO1 / 2022-250 techniques. Examples of techniques that can be used to identify the presence of a malignant polyp can include, without limitation, analyses of histology and degree of dysplasia in the polyp (e.g., via hematoxylin and eosin staining of tissue from a polyp). In some cases, the molecular profile of a polyp can be used to identify the polyp as being likely to recur. For example, the presence of one or more of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increase level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH) in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be used to identify the polyp(s) as being likely to recur. In some cases, the molecular profile of a polyp can be used to identify the polyp as not being likely to recur. For example, the absence of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide)one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH) in a sample (e.g., a sample containing one or more polyp cells) obtained from a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be used to identify the polyp(s) as not being likely to recur. Attorney Docket No.07039-2155WO1 / 2022-250 In some cases, a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) that are assessed as described herein (e.g., to determine whether or not the polyps are or are likely to become malignant and/or likely to recur based, at least in part, on the molecular profile of the polyps) can be selected from one or more treatments where the treatments are selected based, at least in part, on the molecular profile of the mammal’s polyp(s) as described herein. In general, a treatment and/or intervention for one or more polyps (e.g., one or more colon polyps) can include any appropriate polyp treatment and/or intervention. In some cases, a polyp treatment and/or intervention can include surgery (e.g., colectomy and/or lymph node removal) and/or other medical interventions. Examples of treatments and/or interventions that can be used to treat a mammal having one or more polyps can include, without limitation, surgery to remove of the polyp(s) (e.g., polypectomy (e.g., polypectomy with or without injection of a liquid to lift and isolate the polyp from surrounding tissue) such as colonoscopic polypectomy, proctocolectomy (e.g., segmental, subtotal, or total proctocolectomy), regular screenings (e.g., colonoscopies), eating a healthy diet, (e.g., a diet including fruits, vegetables, nuts, seeds, whole grains, omega 3 fatty acid containing foods (e.g., cold water fishes), reduced animal protein, and reduced nitrite preserved foods intake), adopting healthy lifestyle habits (e.g., limited alcohol consumption and limited tobacco usage), physical activity, maintaining a healthy body weight, taking one or more nutritional supplements (e.g., calcium, turmeric, antioxidant, polyphenols, multivitamins, and vitamin D), aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and combinations thereof. In some cases, a mammal (e.g., a human) having at least one polyp (e.g., at least one colon polyp) that is identified as not being or not likely to become malignant and/or not likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyps) can be selected to receive a polyp treatment (e.g., a colon polyp treatment). For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile that lacks an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length), can be selected for one or more colon polyp treatments such as surgery (e.g., colonoscopic polypectomy) to remove the polyps (e.g., in the absence of a cancer treatment). For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile that (a) lacks an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), and (b) contains a wild type KRAS polypeptide (or a nucleic acid encoding a wild type KRAS polypeptide), can be selected for one or more colon polyp treatments that do not include any invasive treatment (e.g., surgery to remove the polyps). In some cases, a mammal (e.g., a human) having at least one polyp (e.g., at least one colon polyp) that is identified as being or likely to become malignant and/or as likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyps) can be selected for more frequent (e.g., additional and/or increased) screenings. For example, a mammal identified as having a malignant polyp and/or a polyp that is likely to recur can be selected for more frequent screenings for the presence or absence of polyps. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile having the presence of one or more of an increased level of an Attorney Docket No.07039-2155WO1 / 2022-250 ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length), can be selected for more frequent (e.g., additional and/or increased) screenings. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile having the presence of one or more of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH), can be selected for more frequent (e.g., additional and/or increased) screenings. In some cases, a mammal (e.g., a human) having at least one polyp (e.g., at least one colon polyp) that is identified as being or likely to become malignant as described herein (e.g., based, at least in part, on the molecular profile of the polyps) can be selected to receive one or more polyp treatments and can be selected for one or more cancer treatments. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are Attorney Docket No.07039-2155WO1 / 2022-250 identified as having a molecular profile having the presence of one or more of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length), can be selected for one or more colon polyp treatments such as surgery to remove the polyp(s) (e.g., polypectomy or colectomy) and, optionally, to receive one or more (e.g., one, two, three, four, five, or more) cancer treatments. This document also provides methods for treating a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps). In some cases, a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) that are assessed as described herein (e.g., to determine whether or not the polyps are or are likely to become malignant and/or likely to recur based, at least in part, on the molecular profile of the polyps) can be administered or instructed to self-administer one or more (e.g., one, two, three, four, five, or more) treatments and/or interventions where the one or more treatments and/or interventions are effective to treat the polyps within the mammal. For example, a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) can be administered or instructed to self-administer one or more treatments and/or interventions selected based, at least in part, on whether or not the polyps are or are likely to become malignant and/or are likely to recur (e.g., based, at least in part, on the molecular profile of the polyps). Attorney Docket No.07039-2155WO1 / 2022-250 When treating a mammal (e.g., a human) having at least one polyp (e.g., at least one colon polyp) that is identified as not being or not likely to become malignant and/or as not being likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyps), the mammal can receive a polyp treatment (e.g., a colon polyp treatment). For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile that lacks an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length), can be subjected to one or more colon polyp treatments such as surgery to remove the polyps (e.g., colonoscopic polypectomy) in the absence of any cancer treatment. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile that (a) lacks an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), and (b) contains a wild type KRAS polypeptide (or a nucleic acid encoding a wild type KRAS polypeptide), can be subjected to one or more colon Attorney Docket No.07039-2155WO1 / 2022-250 polyp treatments that do not include any invasive treatment (e.g., surgery to remove the polyps). In some cases, when treating a mammal (e.g., a human) having a polyp (e.g., a colon polyp) that is identified as not being or not likely to become malignant and/or as not being likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyps), the one or more colon polyp treatments can be the sole treatment used to treat the mammal. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile that lacks an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length) can be subjected to one or more colon polyp treatments (e.g., surgery to remove the polyps such as a colonoscopic polypectomy) and is not administered or instructed to self-administer any cancer treatments. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile that (a) lacks an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and a decreased level of an IGLL5 Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide (or mRNA encoding an IGLL5 polypeptide), and (b) contains a wild type KRAS polypeptide (or a nucleic acid encoding a wild type KRAS polypeptide) can be subjected to one or more colon polyp treatments that that do not include any invasive treatment and is not subjected to any surgery to remove the polyps. When treating a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) that are identified as being or likely to become malignant as described herein (e.g., based, at least in part, on the molecular profile of the polyps), the mammal can be subjected to one or more colon polyp treatments (e.g., surgery to remove the polyps) and can be administered or instructed to self-administer one or more cancer treatments. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified having a molecular profile that includes the presence of one or more of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more chromosomal rearrangements (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs), an increased frequency of LOH, and changes in telomere structure (e.g., telomere content and telomere length) can be subjected to one or more colon polyp treatments (e.g., surgery to remove the polyps) and can be administered or instructed to self-administer one or more (e.g., one, two, three, four, five, or more) cancer treatments. A cancer treatment can include any appropriate cancer treatment. In some cases, a cancer treatment can include surgery and/or other medical interventions. Examples of surgeries and other medical interventions that can be performed on a mammal having one or more polyps (e.g., one or more colon polyps) identified as being or likely to become malignant as Attorney Docket No.07039-2155WO1 / 2022-250 described herein (e.g., based, at least in part, on the molecular profile of the polyps) to treat the mammal include, without limitation, surgery to remove the polyp(s) (e.g., polypectomy (e.g., polypectomy with or without injection of a liquid to lift and isolate the polyp from surrounding tissue), laparoscopy, total proctocolectomy), surgery to remove the tissue around the polyp(s), surgery to remove the polyp(s) and the surrounding tissue, and radiation therapy. In some cases, a cancer treatment can include administering one or more anti-cancer drugs (e.g., chemotherapeutic agents, targeted cancer drugs, and immunotherapy drugs) to a mammal in need thereof. Examples of anti-cancer drugs that can be administered to a mammal having one or more polyps (e.g., one or more colon polyps) identified as being or likely to become malignant as described herein (e.g., based, at least in part, on the molecular profile of the polyps) can include, without limitation, docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab (e.g., Avastin^®), cetuximab (e.g., ERBITUX^®), panitumumab (e.g., Vectibix^®), ramucirumab (e.g., CYRAMZA^®), regorafenib (e.g., Stivarga^®), ziv-aflibercept (e.g., ZALTRAP^®), and combinations thereof. When treating a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) that are identified as being likely to recur as described herein (e.g., based, at least in part, on the molecular profile of the polyps), the mammal can be subjected to one or more colon polyp treatments (e.g., surgery to remove the polyps) and can undergo more frequent (e.g., additional and/or increased) screenings. For example, a mammal having one or more polyps (e.g., one or more colon polyps) that are identified as having a molecular profile having the presence of one or more of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH), can be Attorney Docket No.07039-2155WO1 / 2022-250 subjected to one or more colon polyp treatments (e.g., surgery to remove the polyps) and can be selected for more frequent (e.g., additional and/or increased) screenings. In some cases, when treating a mammal (e.g., a human) having one or more polyps (e.g., one or more colon polyps) as described herein, the treatment can be effective to treat the polyps (e.g., while minimizing the risk of metastasis and/or recurrence). For example, the number of polyps (e.g., colon polyps) present within a mammal can be reduced using the methods and materials described herein. In some cases, the methods and materials described herein can be used to reduce the number of polyps (e.g., colon polyps) present within a mammal having one or more polyps (e.g., one or more colon polyps) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent (e.g., while minimizing the risk of metastasis and/or recurrence). In some cases, the number of polyps (e.g., colon polyps) present within a mammal does not increase. For example, the size (e.g., volume) of one or more polyps (e.g., colon polyps) present within a mammal can be reduced using the methods and materials described herein. In some cases, the methods and materials described herein can be used to reduce the size of one or more polyps (e.g., colon polyps) present within a mammal having one or more polyps (e.g., one or more colon polyps) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent (e.g., while minimizing the risk of metastasis and/or recurrence). In some cases, the size (e.g., volume) of one or more polyps (e.g., one or more colon polyps) present within a mammal does not increase. In some cases, a course of treatment, the number and/or size of one or more polyps (e.g., one or more colon polyps) present within a mammal can be monitored. Any appropriate method can be used to determine whether or not the number and/or size of one or more polyps (e.g., one or more colon polyps) present within a mammal is reduced. For example, imaging techniques can be used to assess the number of polyps present within a mammal. The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

Attorney Docket No.07039-2155WO1 / 2022-250 E^XAMPLES Example 1: Predicting Colorectal Polyp Outcome This Example describes the identification of molecular profiles for polyps that can be used to identify the polyp as malignant and/or to predict whether or not the polyp is likely to recur. Methods Patient sample characteristics and tissue preparation. All tissues were collected as described elsewhere (Druliner et al., Clin. Transl. Gastroenterol., 7(9):e188 (2016)). Polyp tissues with adjacent tumor and normal colonic epithelium full thickness specimens at least 8 cm from the polyp/tumor margin were harvested following surgical resection, were snap frozen in liquid nitrogen, and were maintained in a -80°C freezer. Cancer free polyps and normal colonic epithelium at least 8 cm from the polyp were collected at the time of colonoscopic resection. Cancer adjacent polyp (CAP) and cancer free polyp (CFP) cases were utilized. Cancer adjacent polyps (CAPs) were matched to the cancer free polyps (CFPs) based on polyp size (categorical size: 1 to 2 cm, 2-5 cm, and > 5 cm), histology (villous features), and degree of dysplasia. All polyps presented herein were adenomatous polyps with villous features (tubulovillous or villous), and with low grade dysplasia only. All CAP and CFP cases exclude subjects with a prior history of any malignancy, a family history of Lynch syndrome or FAP, and any other syndrome associated with hereditary CRC or inflammatory bowel disease. All tissue used in these examples was removed prior to neoadjuvant/adjuvant therapy. CAPs were cases in which histological review of the surgically resected CRC showed the residual polyp of origin (RPO) in direct contiguity to the cancer. Peripheral blood leukocytes from the patients were obtained, when possible, prior to removal of the tissue, and any neo-adjuvant/adjuvant treatment. POP categories include non-aggressive non-recurrent (POP-NA), recurrent advanced adenomatous polyp tissues collected at sequential procedures (POP-A), those that develop CRC (POP-CRC). For POP-NA, an advanced adenomatous polyp was initially detected and removed by colonoscopy, and after the recommended colonoscopic surveillance three years post polypectomy, no polyp recurrence was detected at the site of the initial Attorney Docket No.07039-2155WO1 / 2022-250 polypectomy. For all POP categories, the site of initial polypectomy was annotated in the medical record, and was visualized in subsequent colonoscopies by the placement of a tattoo at the initial colonoscopy and/or a scar from the initial polypectomy. The recurrence of the index polyp was confirmed endoscopically by observing the presence of the polyps in the scar from the previous polypectomy or at the site of a tattoo placed at the time of the index polypectomy. The POP-A category refers to an advanced polyp removed by colonoscopy, but which recurred at least once at the site of initial polypectomy and was ultimately cured by colonoscopic polypectomy or surgery. POP-NA had the lowest degree of aggressiveness, followed by the POP-A category. The highest degree of aggressiveness was reserved for POP-CRC in which recurrent polyps were removed but developed cancer at the site of initial and subsequent polypectomies or present with cancer. Tissues were macro-dissected using a hematoxylin and eosin (H&E) guide that was used to mark areas of normal epithelium, polyp, or cancer by a pathologist. DNA and RNA was extracted using the Maxwell^® RSC Instrument and appropriate kits (Promega) from all tissues and quantitated using a Qubit Fluorometer. Telomere dynamics measurement and analysis TelomereHunter software claimed strong correlation with corresponding monochrome multiplex real-time quantitative PCR (mmqPCR) telomere lengths. TelomereHunter was run on all WGS samples and resulting telomere content variable was used as a proxy for telomere length in the prediction model. Whole Genome Sequencing (WGS) and RNA-seq DNA libraries were prepared at BGI from 10 ng input genomic DNA (representing roughly 2000 nuclei) from each tissue using the NEB kit (NEBNext^® Ultra™ II FS DNA Library Prep Kit for Illumina. Samples were sequenced on the BGISEQ500 by 100 bp paired end. RNA-seq was performed using a Eukaryotic Transcriptome Library Construction Protocol and an RNase H method for library prep, and libraries were sequenced on HiseqXten by 150 bp paired end. Attorney Docket No.07039-2155WO1 / 2022-250 WGS, RNA-Seq processing and analyses WGS data was processed using the Picard Informatics Pipeline, with all data from a particular sample aggregated into a single BAM file which included all reads, all bases from all reads, and original/vendor-assigned quality scores. A pooled Variant Call Format (VCF) file using the latest version of Picard GATK software was generated and provided for each sample batch. Data for RNA-seq was analyzed using the Broad Picard Pipeline, which includes de-multiplexing and data aggregation. MAP-RSeq is an integrated RNA-Seq bioinformatics pipeline developed for comprehensive analysis of raw RNA sequencing paired-end reads. MAP-RSeq employs STAR, a splice-aware, accurate and fast aligner for aligning reads to the reference human genome (build hg38). Gene and exon expression quantification was performed using Subread package to obtain raw and normalized (FPKM – Fragments Per Kilobase per Million mapped) reads. Comprehensive quality control modules from the RSeQC package were run on aligned reads to assess the quality of the sequenced libraries. ComBat-seq was used to normalize and remove batch effects between sets A and B. Raw counts generated by ComBat-seq were used for performing differential gene expression analysis between CAP and CFP groups using R package edgeR. The criteria for selection of significant differentially expressed (DE) genes were: | log2 fold change | > 1 and Benjamini- Hochberg adjusted p-value < 0.05. Volcano plots and PCA visualization were generated using R package ggplot2, and heatmaps were generated using R packages pheatmap and gplots. DE protein coding genes were analyzed using UMAP to determine top genes that contribute most toward differentiating CAP and CFP classes. CIBERSORT CIBERSORT’s LM22 signature was used to determine the immune composition in all RNA sequencing samples. Each cell type was tested for differential distribution between CAP and CFP classes using two sample T-test. SASP expression Using RNA-seq data here, gene expression of a panel of genes related to senescence- associated secretory phenotype (SASP) was determined in each of the polyp tissues. Attorney Docket No.07039-2155WO1 / 2022-250 Machine learning model development For the CAP/CFP model: A total of 141 polyps across discovery and validation sets were used for CAP vs CFP binary classification. The cohort was split 80/20 into training set (112 samples) and test (29 samples) set. Model features were tested for multicollinearity and features with Pearson correlation less than 0.90 were retained. Robust QuantileTransformer was used to scale input features. AutoGluon was run on training set with bagging and multi- layer stack ensembling options switched to auto-stacking which allowed AutoGluon to determine optimum number of folds and repeats of cross-fold validation. AutoGluon’s default 80/20 split was used for setting training/validation sets with positive class defined as CAP. Evaluation metric was set to ‘roc_auc’ and presets were set to ‘best_quality’. The best performing model was evaluated on the test set of 29 samples after re-fitting to the entire training set. For POP-R/POP-NR model, the initial 53 training samples (3 were removed during model cross-validation due to lack of paired blood/epithelium normal samples) were evenly split into 5 sub-cohorts using set and status variables (stage variable was not used due to small sample size). Features were selected using criteria employed for CAP/CFP feature selection step. KRAS mutations were also used as candidate features. Model feature selection Differential gene expression was performed on 112 training samples by further splitting the training cohort into 5 sets with each set containing 80% samples. This split was performed using set (Discovery/Validation), status (CAP/CFP), and stage (villous/tubular) variables to ensure even distribution in the 5 sub-cohorts. Significance thresholds were defined as log2FC > |1| and BH adjusted p-value < 0.05. Batch corrected normalized values (CPM, count per million) of top 10 protein coding genes in at least 3 out of 5 sub-cohorts were selected as input gene features for respective models. In addition to individual gene expression levels, Cibersort features were tested for significance. Among genomic features, telomere lengths derived from TelomereHunter and CNV levels (DUP, DEL and LOH scores) generated using CNVpytor were also used as input features to the model. Attorney Docket No.07039-2155WO1 / 2022-250 Statistical Analysis Wilcoxon rank-sum test was used to test for statistical differences between groups. Analyses were performed as a comparison between all CAPs and CFPs, where there was one polyp tissue per each patient within the groups. The criteria for selection of significant differentially expressed (DE) genes were: log2 fold change > |1| and Benjamini-Hochberg adjusted p-value < 0.05. All plots and statistical analyses were performed using R software (R 4.0.3). Software packages include: ggsignif, ggplot2, CMScaller, WGCNA, sva, tidyr, DESeq2, EnhancedVolcano, pheatmap, GSVA, GSEABase, ggpubr, dplyr, ggbeeswarm, rstatix, tidyverse, data.table, stringr, colorRamps, circlize, gtools, edgeR, tibble, fgsea, rbibutils, knitr, ComplexHeatmap. KEGG pathway enrichment was determined by the p- value of the hypergeometric test via ShinyGO 0.76 using differential genes identified as described herein. Patient-derived organoids Organoids were generated using procedures for the isolation of crypts from fresh normal colon tissue. Briefly, crypts were released from freshly collected tissue using 5 mM EDTA, rocking at 4°C for 60-75 minutes. After isolation, crypts were embedded in ice-cold Matrigel (Corning^® Matrigel^® Growth Factor Reduced Product #356231), plated in 24-well plates and overlaid with Human Colon Media. Organoids were passaged using TrypLE digestion every 7-10 days. Human Colon Media contains 50% Wnt, Noggin and R-Spondin (WRN) obtained from conditioned media from the L-WRN cell line (ATCC). Other growth factors were added to this media including: N2 supplement (1X; Gibco), B27 supplement (1X, Gibco), EGF (40 ng/mL, R&D Systems), SB202190 (3 ?M, Sigma), A83-01 (500 nM, Tocris), Y-27632 (10 ?M, APExBio), NAC (1 ?M, Sigma), Nicotinamide (10 mM, Sigma), Gastrin I (10 nM, Sigma), Primocin (100 ?g/mL, Invivogen), and Antibiotic/Antimycotic (1X, Fisher). Human Colon Media for culturing organoids and gene editing details ADMEM base media contains 50% Wnt, Noggin and R-Spondin (WRN) obtained from conditioned media from the L-WRN cell line (ATCC). Other growth factors are added to this media including: N2 supplement (1X; Gibco), B27 supplement (1X, Gibco), EGF (40ng/mL, R&D Systems), SB202190 (3 ?M, Sigma), A83-01 (500 nM, Tocris), Y-27632 Attorney Docket No.07039-2155WO1 / 2022-250 (10 ?M, APExBio), NAC (1 ?M, Sigma), Nicotinamide (10 mM, Sigma), Gastrin I (10 nM, Sigma), Primocin (100 ?g/mL, Invivogen), Antibiotic/Antimycotic (1X, Fisher). hTERT was cloned downstream of the CMV promoter followed by a stop codon and a rabbit beta globin poly adenylation sequence. Downstream of the TERT cassette, the vector also contained an EF1? promoter expressing GFP and puromycin resistance genes separated by a 2A peptide (2 ?g/ml puromycin to the organoid medium for at least 2 days or indefinitely). Overexpression of hTERT using gene editing in organoids A transposon based method was used for gene editing in the human colon organoids, using piggyBac vectors gene electrotransfer (electroporation) as the method for cargo delivery to the organoids. PiggyBac transposon (System Biosciences Cat. # PB513B-1) vector containing an hTERT construct was used (Addgene plasmid #1774). hTERT was driven by the CMV promoter and then had a stop codon followed immediately by an EF1A promoter expressing the GFPT2APuro portion. This enabled the simultaneous visualization of transfection and editing efficiency, followed by selection via puromycin (add 2 ?g/mL puromycin to the organoid medium for at least 2 days or indefinitely). The NEPA21 Electroporator (NEPA GENE) was used for cargo delivery. Integration of the cargo was verified by copy number detection, quantitative PCR (using HeLa cell as a telomerase positive control and normalized to GAPDH), and RNA-seq. RNAscope Formalin fixed paraffin embedded (FFPE) tissues were obtained and sectioned at a thickness of 5 ?m and mounted on the SuperFrost^® Plus slides (Fisherbrand Cat #12-550-15). Ready-to-use reagents from RNAscope™ HiPlex12 Reagents Kit (488, 550, 650) v2 (Advanced Cell Diagnostics #322350) were used according to the user manual (Document Number UM 324419). FFPE tissue sections were baked and deparaffinized, followed by target retrieval and protease III treatment (15 minutes at 40°C). RNAscope^® HiPlex Probes targeting the human SFRP2, THBS2, SERPINE1, CYR61, and ADAMTS4 mRNA were used. Probe hybridization, signal amplification, colorimetric detection, and counterstaining were subsequently performed. Following DAPI stain, the cells were mounted and imaged using confocal microscope. Attorney Docket No.07039-2155WO1 / 2022-250 Results Molecular features distinguish CAPs and CFPs in a validated cohort To molecularly characterize polyps, cancer adjacent polyp (CAP) and cancer free polyp (CFP) cases were utilized (Figure 1A). A discovery set using telomere length, telomere maintenance mechanisms, genetic, transcriptional and methylation profiles distinguish CFPs and CAPs as described elsewhere (Druliner et al., Clin. Transl. Gastroenterol., 7(9):e188 (2016)) was used. Findings of a discovery set were validated in an independent cohort of 100 patients (the validation set), all of which represent advanced adenomatous polyps. Patient demographics for this cohort can be found in Table 1. Whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) were performed on normal colon, polyp and cancer tissues from 50 CFPs and 50 CAPs (Figure 1A). Somatic mutation prevalence (Figure 1B), copy number variant (CNV) mean event size (Figure 1C), differential gene expression (Figure 1D and Example 2), KEGG pathway enrichment (Figure 1E), telomere length (Figure 1F), and the telomere maintenance mechanism of hTERT based on expression (Figure 1G) were differential between CFPs and CAPs, and consistent between the discovery and validation sets. Gene expression analysis revealed 794 genes that were differentially expressed between CAPs and CFPs (Figure 1D), with an exemplary gene, GREM1, showing higher expression in the CAP category in both discovery and validation sets. The genes that were up-regulated in CAPs compared to CFPs were enriched in pathways related to protein digestion and absorption, viral infection, focal adhesion, PI3K-Akt pathway, and transcriptional misregulation in cancer (Figure 1E). CAPs had significantly more mutations, altered expression, longer telomeres, and greater hTERT expression than CFPs. Table 1. Clinical phenotypes of Specimens CAP CRC or POP- Date of Stage; Patient Age Gender CFP Category Tissue Type Index polyp % tumor CRC/Polyp location B01 52 Male CAP CAP ADCA70 9/11/2006 II; 70 Ascending B01 52 Male CAP CAP POLYP (T5L) B01 52 Male CAP CAP NEAR NORMAL Attorney Docket No.07039-2155WO1 / 2022-250 B02 73 Female CAP CAP ADCA80 11/26/2012 II; 80 Transverse & Sigmoid B02 73 Female CAP CAP POLYP (T0L) B02 73 Female CAP CAP NEAR NORMAL B03 82 Female CAP CAP ADCA80 3/18/2013 I; 80 Ascending B03 82 Female CAP CAP POLYP (T10H) B03 82 Female CAP CAP NEAR NORMAL B04 74 Female CAP CAP ADCA60 2/8/2011 IV; 60 Ileocecal Valve B04 74 Female CAP CAP POLYP (T0L) B04 74 Female CAP CAP NEAR NORMAL B05 71 Male CAP CAP ADCA 10/26/2000 IV; U/K Cecum B05 71 Male CAP CAP POLYP (T0L) B05 71 Male CAP CAP DISTAL NORMAL B06 69 Female CAP CAP ADCA 3/21/2012 IV; U/K Cecum B06 69 Female CAP CAP POLYP (V40L) B06 69 Female CAP CAP DISTAL NORMAL B07 75 Male CAP CAP ADCA50 2/11/2004 III; 50 Rectum B07 75 Male CAP CAP POLYP (T0L) B07 75 Male CAP CAP DISTAL NORMAL B08 67 Female CAP CAP ADCA 5/25/2007 IV; U/K Cecum B08 67 Female CAP CAP POLYP (V30L) B09 69 Female CAP CAP ADCA80 4/18/2007 I; 80 Ascending B09 69 Female CAP CAP POLYP (T5L) B10 76 Male CAP CAP ADCA60-70 11/26/2001 IV; 60-70 Rectum B10 76 Male CAP CAP POLYP (T0L) B10 76 Male CAP CAP PBL B11 67 Male CAP CAP ADCA70 5/28/2004 IV; 70 Rectum B11 67 Male CAP CAP POLYP (TSA 80L) B11 67 Male CAP CAP PBL B12 63 Female CAP CAP ADCA80 8/9/2004 III; 80 Ileocecal Valve B12 63 Female CAP CAP POLYP (T0L) B12 63 Female CAP CAP DISTAL NORMAL B13 68 Male CAP CAP ADCA 9/3/2003 II; U/K Ascending & Sigmoid B13 68 Male CAP CAP B13 68 Male CAP CAP B14 46 Female CAP CAP 9/17/2004 IV; U/K Rectum B14 46 Female CAP CAP B14 46 Female CAP CAP B15 57 Female CAP CAP 9/27/2007 IV; U/K Ascending B15 57 Female CAP CAP B15 57 Female CAP CAP B16 66 Male CAP CAP 11/23/2001 II; 60 Cecum B16 66 Male CAP CAP B16 66 Male CAP CAP B17 86 Male CAP CAP 12/23/2002 III; 50-60 Transverse B17 86 Male CAP CAP Attorney Docket No.07039-2155WO1 / 2022-250 B17 86 Male CAP CAP DISTAL NORMAL B18 88 Male CAP CAP ADCA80 9/18/2003 IV; 80 Rectum B18 88 Male CAP CAP POLYP (T0H) B18 88 Male CAP CAP DISTAL NORMAL B19 74 Female CAP CAP ADCA80 8/30/2007 IV; 80 Ascending B19 74 Female CAP CAP POLYP (V30L) B19 74 Female CAP CAP DISTAL NORMAL B20 85 Female CAP CAP ADCA 9/29/2005 IV; U/K Cecum B20 85 Female CAP CAP POLYP (V40H) B20 85 Female CAP CAP DISTAL NORMAL B21 53 Female CAP CAP ADCA80 7/11/2012 III; 80 Descending B21 53 Female CAP CAP POLYP (T0H) B21 53 Female CAP CAP DISTAL NORMAL B22 61 Male CAP CAP ADCA60 9/7/2000 I; 60 Cecum B22 61 Male CAP CAP POLYP (T5L) B22 61 Male CAP CAP DISTAL NORMAL B23 87 Male CAP CAP ADCA80 12/6/2005 III; 80 Rectum B23 87 Male CAP CAP POLYP (T0L) B23 87 Male CAP CAP DISTAL NORMAL B24 80 Female CAP CAP ADCA80 4/19/2001 III; 80 Ascending B24 80 Female CAP CAP POLYP (T10L) B24 80 Female CAP CAP DISTAL NORMAL B25 54 Female CAP CAP ADCA60 8/11/2011 IV;60 Cecum B25 54 Female CAP CAP POLYP (V50L) B25 54 Female CAP CAP DISTAL NORMAL B26 49 Male CAP CAP ADCA70 5/12/2005 III; 70 Sigmoid B26 49 Male CAP CAP POLYP (T0L) B26 49 Male CAP CAP DISTAL NORMAL B27 72 Male CAP CAP ADCA70 4/22/2009 III; 70 Ascending B27 72 Male CAP CAP POLYP (V30L) B27 72 Male CAP CAP DISTAL NORMAL B28 52 Female CAP CAP ADCA60 5/5/2009 III; 60 Sigmoid B28 52 Female CAP CAP POLYP (T10L) B28 52 Female CAP CAP DISTAL NORMAL B29 73 Male CAP CAP ADCA70 1/24/2005 III; 70 Rectosigmoid B29 73 Male CAP CAP POLYP (T5L) B29 73 Male CAP CAP DISTAL NORMAL B30 54 Male CAP CAP ADCA 3/23/2007 III; U/K Cecum B30 54 Male CAP CAP POLYP (T0L) B30 54 Male CAP CAP DISTAL NORMAL B31 74 Female CAP CAP ADCA80 2/24/2012 III; 80 Cecum B31 74 Female CAP CAP POLYP (V30L) B31 74 Female CAP CAP DISTAL NORMAL B32 73 Female CAP CAP ADCA70 1/19/2007 III; 70 Cecum B32 73 Female CAP CAP POLYP (T10L) B32 73 Female CAP CAP PBL B33 80 Female CAP CAP ADCA60 1/27/2012 II; 60 Cecum Attorney Docket No.07039-2155WO1 / 2022-250 B33 80 Female CAP CAP POLYP (T10L) B33 80 Female CAP CAP PBL B34 74 Male CAP CAP ADCA60-50 10/31/2002 III; 60-50 Cecum B34 74 Male CAP CAP POLYP (T0L) B34 74 Male CAP CAP PBL B35 63 Male CAP CAP ADCA60 10/22/2002 III; 60 Sigmoid B35 63 Male CAP CAP POLYP (T0L) B35 63 Male CAP CAP DISTAL NORMAL B36 59 Female CAP CAP ADCA70 5/4/2005 III; 70 Cecum B36 59 Female CAP CAP POLYP (T20L) B36 59 Female CAP CAP DISTAL NORMAL B37 63 Male CAP CAP ADCA 11/5/2003 II; U/K Sigmoid B37 63 Male CAP CAP POLYP (T0H) B37 63 Male CAP CAP DISTAL NORMAL B38 39 Female CAP CAP ADCA60 5/9/2011 II; 60 Sigmoid B38 39 Female CAP CAP POLYP (V30L) B38 39 Female CAP CAP DISTAL NORMAL B39 79 Male CAP CAP ADCA 9/7/2004 II; U/K Cecum B39 79 Male CAP CAP POLYP (V30L) B39 79 Male CAP CAP DISTAL NORMAL B40 71 Female CAP CAP ADCA 3/24/2009 II; U/K Ascending B40 71 Female CAP CAP POLYP (V40L) B40 71 Female CAP CAP DISTAL NORMAL B41 62 Female CAP CAP ADCA70 12/23/2010 I; 70 Ascending B41 62 Female CAP CAP POLYP (V30L) B41 62 Female CAP CAP DISTAL NORMAL B42 42 Male CAP CAP ADCA80 5/22/2013 II; 80 Cecum B42 42 Male CAP CAP POLYP (T10H) B42 42 Male CAP CAP DISTAL NORMAL B43 70 Male CAP CAP ADCA50 6/7/2005 II; 50 Cecum B43 70 Male CAP CAP POLYP (T5L) B43 70 Male CAP CAP DISTAL NORMAL B44 56 Male CAP CAP ADCA70-80 7/19/2007 III; 70-80 Sigmoid B44 56 Male CAP CAP POLYP (T0-5H) B44 56 Male CAP CAP DISTAL NORMAL B45 49 Male CAP CAP ADCA80 8/24/2005 III; 80 Cecum B45 49 Male CAP CAP POLYP (V30L) B45 49 Male CAP CAP DISTAL NORMAL B46 73 Male CAP CAP ADCA 1/26/2004 II; U/K Ascending B46 73 Male CAP CAP POLYP (T5H) B46 73 Male CAP CAP DISTAL NORMAL B47 69 Male CAP CAP ADCA80 2/17/2012 I; 80 Ascending B47 69 Male CAP CAP POLYP (T0L) B47 69 Male CAP CAP DISTAL NORMAL B48 60 Male CAP CAP ADCA70 4/16/2013 III; 70 Rectum B48 60 Male CAP CAP POLYP (T5H) B48 60 Male CAP CAP DISTAL NORMAL Attorney Docket No.07039-2155WO1 / 2022-250 B49 68 Female CAP CAP ADCA60 9/15/2007 III; 60 Rectosigmoid B49 68 Female CAP CAP POLYP (T0L) B49 68 Female CAP CAP DISTAL NORMAL B50 71 Male CAP CAP ADCA70 6/15/2006 III; 70 Ascending B50 71 Male CAP CAP POLYP (T10-0H) B50 71 Male CAP CAP DISTAL NORMAL B51 69 Male CFP POP-NR POLYP (T0L) 3/28/2002 Transverse B51 69 Male CFP POP-NR DISTAL NORMAL B52 61 Male CFP POP-NR POLYP (T0L) 11/30/2000 Cecum B52 61 Male CFP POP-NR DISTAL NORMAL B53 84 Female CFP POP-R POLYP (T0L) 4/18/2011 Rectum B53 84 Female CFP POP-R DISTAL NORMAL B54 53 Female CFP POP-R POLYP (V40L) 10/10/2007 Sigmoid B54 53 Female CFP POP-R PBL B55 44 Female CFP POP-R POLYP (T15L) 5/15/2007 Cecum B55 44 Female CFP POP-R PBL B56 72 Female CFP POP-R POLYP (T0L) 3/8/2001 Rectum B56 72 Female CFP POP-R PBL B57 66 Male CFP POP-R POLYP (T0L) 7/22/2005 Sigmoid B57 66 Male CFP POP-R PBL B58 75 Male CFP POP-R POLYP (T0L) 9/13/2001 Cecum B59 71 Female CFP POP-R POLYP (T5L) 6/25/2010 Rectum B60 49 Male CFP POP-R POLYP (V50L) 3/1/2004 Rectosigmoid B60 49 Male CFP POP-R PBL B61 75 Male CFP POP-R POLYP (V30L) 2/8/2012 Ascending B61 75 Male CFP POP-R PBL B62 83 Male CAP CAP POLYP (T0L) 1/18/2011 Hepatic Flexure B62 83 Male CAP CAP PBL B63 68 Male CFP POP-R POLYP (T0L) 12/17/2004 Ascending B63 68 Male CFP POP-R PBL B64 70 Male CFP POP-NR POLYP (T20L) 11/28/2000 Sigmoid B64 70 Male CFP POP-NR PBL B65 62 Male CFP POP-R POLYP (V50L) 3/30/2001 Rectum B65 62 Male CFP POP-R PBL B66 61 Female CFP POP-R POLYP (V50L) 7/14/2005 Cecum B66 61 Female CFP POP-R PBL B67 70 Female CFP POP-R POLYP (V80L) 1/20/2006 Rectosigmoid B67 70 Female CFP POP-R PBL B68 67 Male CFP POP-R POLYP (V50L) 1/7/2009 Hepatic Flexure B68 67 Male CFP POP-R PBL B69 65 Male CFP POP-R POLYP (T5L) 10/24/2003 Transverse B69 65 Male CFP POP-R DISTAL NORMAL B70 73 Male CFP POP-R POLYP (V40L) 5/29/2007 Cecum B70 73 Male CFP POP-R DISTAL NORMAL Attorney Docket No.07039-2155WO1 / 2022-250 B71 72 Male CFP POP-NR POLYP (T0L) 4/20/2009 Ascending B71 72 Male CFP POP-NR DISTAL NORMAL B72 75 Male CFP POP-R POLYP (V50L) 10/27/2009 Transverse B72 75 Male CFP POP-R DISTAL NORMAL B73 62 Female CFP POP-R POLYP (T0L) 3/21/2006 Transverse B73 62 Female CFP POP-R DISTAL NORMAL B74 59 Male CFP POP-R POLYP (T20H) 4/22/2008 Cecum B74 59 Male CFP POP-R DISTAL NORMAL B75 65 Female CAP POP-CRC POLYP (SSA) 7/3/2001 Transverse B75 65 Female CAP POP-CRC DISTAL NORMAL B76 71 Male CFP POP-NR POLYP (T10L) 12/11/2013 Cecum B76 71 Male CFP POP-NR PBL B77 69 Male CFP POP-NR POLYP (V50L) 7/23/2012 Sigmoid B77 69 Male CFP POP-NR PBL B78 44 Female CFP POP-R POLYP (V40L) 8/5/2004 Rectosigmoid B78 44 Female CFP POP-R PBL B79 65 Female CFP POP-NR POLYP (V30L) 3/4/2014 Ascending B79 65 Female CFP POP-NR PBL B80 73 Female CFP POP-NR POLYP (V30L) 2/12/2003 Splenic Flexure B80 73 Female CFP POP-NR PBL B81 85 Female CFP POP-NR POLYP (T5L) 11/23/2004 Rectosigmoid B81 85 Female CFP POP-NR PBL B82 56 Male CFP POP-R POLYP (T5L) 2/2/2012 Ascending B82 56 Male CFP POP-R DISTAL NORMAL B83 77 Male CFP POP-NR POLYP (T5L) 8/14/2001 Rectum B83 77 Male CFP POP-NR DISTAL NORMAL B84 49 Male CFP POP-NR POLYP (T5L) 8/23/2000 Rectum B84 49 Male CFP POP-NR DISTAL NORMAL B85 54 Male CFP POP-NR POLYP (T0L) 1/5/2001 Rectum B85 54 Male CFP POP-NR DISTAL NORMAL B86 58 Male CFP POP-NR POLYP (T0L) 10/23/2003 Sigmoid B86 58 Male CFP POP-NR DISTAL NORMAL B87 56 Male CFP POP-NR POLYP (T0L) 2/6/2008 Splenic Flexure B87 56 Male CFP POP-NR DISTAL NORMAL B88 43 Female CFP POP-NR POLYP (T5L) 4/19/2001 Sigmoid B88 43 Female CFP POP-NR DISTAL NORMAL B89 58 Male CFP POP-NR POLYP (T0L) 4/1/2003 Transverse B89 58 Male CFP POP-NR DISTAL NORMAL B90 53 Male CFP POP-NR POLYP (T20L) 1/27/2004 Ascending B90 53 Male CFP POP-NR DISTAL NORMAL B91 68 Male CFP POP-NR POLYP (V40L) 3/6/2001 Ascending/Hepatic Flexure B91 68 Male CFP POP-NR DISTAL NORMAL B92 62 Male CFP POP-R POLYP (V30L) 1/19/2006 Rectum Attorney Docket No.07039-2155WO1 / 2022-250 B92 62 Male CFP POP-R DISTAL NORMAL B93 77 Female CFP POP-NR POLYP (T0L) 4/3/2001 Rectum B93 77 Female CFP POP-NR DISTAL NORMAL B94 51 Male CFP POP-NR POLYP (T0L) 1/14/2002 Descending B94 51 Male CFP POP-NR DISTAL NORMAL B95 56 Male CFP POP-NR POLYP (T0L) 2/24/2004 Transverse B95 56 Male CFP POP-NR DISTAL NORMAL B96 73 Female CFP POP-R POLYP (V30L) 11/9/2000 Cecum B96 73 Female CFP POP-R DISTAL NORMAL B97 66 Male CFP POP-NR POLYP (T0L) 6/30/2008 Ascending B97 66 Male CFP POP-NR DISTAL NORMAL B98 60 Male CFP POP-NR POLYP (T0L) 10/5/2006 Sigmoid B98 60 Male CFP POP-NR DISTAL NORMAL B99 66 Male CFP POP-NR POLYP (V30L) 3/14/2001 Sigmoid B99 66 Male CFP POP-NR DISTAL NORMAL B100 70 Male CFP POP-R POLYP (V30-60L) 9/12/2001 Rectum B100 70 Male CFP POP-R DISTAL NORMAL Senescence-associated secretory phenotype (SASP) genes are enriched in CAPs Transcriptional data were analyzed to evaluate whether senescence- and SASP- associated pathways were enriched in either CAPs or CFPs. A SASP gene set was examined, indicating that CAP cases showed high expression of SASP genes, while the majority of CFPs had low SASP expression (FIG.2A and Table 3). A Gene Set Enrichment (GSEA)- based approach confirmed increase expression of SASP genes in CAP cases (FIG.2B). These results indicated that expression of SASP genes was increased and enriched in the polyps that progressed to cancer. Table 3. Best CAP vs CFP models ordered by cross-validated AUROC. Model Auto-stacking CV AUROC

Attorney Docket No.07039-2155WO1 / 2022-250 KNeighborsUnif_BAG_L1 0.939394 RandomForestEntr_BAG_L1 0.931818

hTERT overexpression in patient-derived organoid is associated with features that distinguish CAP and CFP cases The telomere maintenance mechanism of telomerase was modified by overexpressing hTERT, the catalytic subunit of telomerase, in an organoid system. An organoid line derived from normal colon tissue collected during surgery for a stage T2 N1b M0 pMMR ascending colon cancer was utilized. A piggyBac transposon system was used to integrate the hTERT gene, along with GFP and a puromycin resistance gene, into the normal human colon organoid line to generate TERT overexpression (TERT+) (Figure 3A, Figure 8A). There was an integration of over 11 copies of the hTERT in the organoids (Figure 8B). qPCR showed TERT expression was nearly 1000-fold higher in the edited organoids compared to an unedited organoid line (Figure 3B). RNA-seq was performed on the unedited and TERT⁺ organoid lines to determine global gene expression changes in the presence of TERT overexpression. Overexpression of TERT in the TERT⁺ organoid line compared to unedited was verified (Figure 3C). The top 200 most highly confidently differentially expressed genes (DEGs) in the organoids (more than 50% difference of the max expression between TERT⁺ and unedited with the greatest difference in log2fold change) were identified and a GSEA was performed on the polyp RNA-seq data with a mean CPM > 0.1. The GSEA showed strong enrichment of the TERT⁺ DEGs in CAP polyps compared to CFP (Figure 3D). KEGG pathways in the TERT⁺ organoids were viral infection, lysosome, circadian rhythm, and inflammation related genes (Figure 3E), many of which also overlapped with the CAP vs CFP DEGs pathways shown in Figure 1D. Genes that were downregulated in the TERT⁺ organoids were enriched for pathways including metabolism, cell cycle, WNT signaling and DNA repair and damage related genes (Figure 9). Although an upregulation of SASP-related genes and increased TERT expression was seen in CAPS, distinct SASP-related genes were either under or over- expressed in TERT⁺ organoids relative to unedited organoids (Figure 3F). Attorney Docket No.07039-2155WO1 / 2022-250 Table 4. Feature importance for CAP vs CFP models. importance p_value tel.content 0.016186 0.001003

Specific immune cell populations distinguish CAP and CFP CIBERSORT was used to derive cell type proportions from bulk RNA sequencing. Immune cell subtypes were derived using CIBERSORT. Specific immune populations differed significantly between CAP and CFPs, with an enrichment of multiple immune cell types in CAPs (Figure 2C). Specifically, the signature for activated mast cells (Figure 2C, top; p-value of 1.382c-06), resting natural killer cells (Figure 2C, bottom; p-value of 5.419e- 10), resting CD4 memory cells (Figure 7A; p-val = 0.00018), and macrophages M0 (Figure 7B; p-val = 0.00664) were all enriched in CAP tissues. Polyps exhibit molecular features that are distinct based on age of onset While most of the polyp and CRC patients in the discovery and validation cohorts represented the average age of onset for CRC (>50 years old), a subset of patients had early age of onset for colorectal neoplasia (?50 years old). There were no overall significant molecular differences between early and average age of onset polyps based on genetic or expression data. Similarly, the molecular distinctions between CAPs and CFPs from the entire cohort were the same when evaluating only the early onset polyp patients. In the polyps of patients <50 years old (CAPs: n=7, CFPs: n=9), CFPs have the shortest telomeres, Attorney Docket No.07039-2155WO1 / 2022-250 while CAPs have longer telomeres, each with distinct gene expression clusters, which is consistent with the average age of onset cohort (Figure 2D). Multiomics Machine Learning Model identifies signature that distinguishes a cancerous from a non-cancerous polyp It was next sought to integrate multiomics features in a machine learning framework to predict whether a polyp would progress to cancer (Figure 4A). SHapley Additive exPlanations (SHAP) python package was used for exploring model output and visualizing feature importance (Figure 4B). The results of 14 models run by AutoGluon were compared by using cross-validation area under the receiver operator characteristic (AUROC) score in the training cohort (Table 3). WeightedEnsemble_L2 was found to be the best performing model with AUROC= 0.9621. The model included the following features: transcriptomic (ADAMTS4, THBS2, SERPINE1, FAP, CYR61, SOX11, CXCL13, SFRP2, and VIP), CIBERSORT (NKC resting phase), and genomic (DUP, DEL, LOH, and telomere content) (Figure 4C, Table 4). Positive predictive value (PPV) was 87.5%, while negative predictive value (NPV) was 84.61%. The predictive accuracy of top significant differentially expressed genes was further tested without using other genomic/transcriptomic features. On testing this model on a hold-out test set, AUROC was 0.9134 [0.8059, 1], PPV = 85.71% and NPV = 73.33%. A set of genes identified as predictive of outcome were then evaluated using RNAscope to visually detect genes that were predictive in tissues from a third cohort of CAP and CFP cases. As an exemplary case, Figure 10 shows THBS2 mRNA expression in CFP (left) and CAP (right) tissues, from two patients that were not included in the Discovery or Validation cohorts, for an independent assessment of detecting differential expression of these genes at the tissue level between a CFP and CAP. Detection of expression was seen only in CAP tissues (n=3). There was poor detection of fluorescence observed for any of the five genes in the CFP tissues (n=3). Refining polyp classification: polyp outcome phenotypes (POP) CFPs were subdivided into two POPs: polyps that did not recur after initial polypectomy (POP-NR) and those that were aggressive and/or did recur but were cured by colonoscopy (POP-R) (Figure 5A). Somatic mutation prevalence (Figure 5B), copy number Attorney Docket No.07039-2155WO1 / 2022-250 variation (Figure 5C), and gene expression (Figure 5D and Example 3) vary between the POP categories and CAPs The most significant difference was between the POP-NR and CAP categories. KEGG pathway analysis on DEGs showed greater overlap between POP-R and categories (Figure 5E). As in Figure 1D, genes enriched in protein digestion and absorption, viral and inflammation related pathways were primarily restricted to CAP cases and not seen in CFPs, regardless of POP status (top four rows in Figure 5E). Genes enriched in metabolism-related pathways were related to CFPs, but most prominently the POP-NR cases. Genes enriched in immune response and inflammation (allograft rejection) and specific cascade pathways (complement and coagulation cascade) were present overall in CAPs and POP-R cases but not in POP-NR (bottom three rows in Figure 5E). Telomere length (Figure 5F) and hTERT expression (Figure 5G) were differential between POP categories, and highest in CAPs. KRAS mutations differentiate recurrent from non-recurrent polyps Somatic KRAS mutations were differentially abundant between POP-NR and POP-R categories (p-val=0.0006726; Fisher’s test). KRAS mutations were only present in 20% of POP-NR cases, whereas they were present in 64.5% and 52.3% of POP-R and CAP cases, respectively (Figure 6A, Table 6). These mutations represented several missense mutations (Example 4). KRAS mutation status amongst the POP-R cases was associated with transcriptomic differences in 328 genes associated with a log2FC> |1|, and BH adjusted pval < 0.05 (Figure 6B and Example 5). Top protein coding genes that were differentially regulated were OBSL1, IGFB5, CCL11, ZNF134 and COL6A1, and all were downregulated in the POP-R KRAS mutated group. Among the POP-R KRAS wildtype cases and the POP-NR cases -the majority of which were also KRAS wildtype, 360 genes with log2FC > |1| and BH adjusted pval < 0.05 (Figure 6C and Example 6). ACTG2, DES, MYL9, CNN1, and MFAP4 were the top protein coding genes and were upregulated in POP-R KRAS wildtype group. Integrating multiomic features into a model to predict polyp recurrence The top distinguishing features between POP-R and POP-NR groups, were used to develop a model to predict whether or not a cancer free polyp would recur. Discovery and validation sets were split 80/20 into 50 training samples and 14 test samples. Owing to small Attorney Docket No.07039-2155WO1 / 2022-250 training set size, we selected simple logistic regression model for binary classification of POP-R vs POP-NR. The model uses saga optimization algorithm, and both I1 and I2 penalty terms (elasticnet, l1 ratio set to 0.5) to avoid overfitting.5-fold cross validation was performed using the training set of 50 samples and this model was applied to the test set without performing further hyperparameter tuning to avoid overfitting to the limited training set. Feature importance was calculated and non-contributory features (coefficient=0) were removed from the final model (Figure 11). This resulted in retaining DE genes (TPRG1, LY6G6C, DUSP4, ZIC5, CYP1A1, and DMKN), KRAS mutations, and CNV features (LOH and DEL) (Figure 6D). Using these features, the final model was run through 5-fold cross validation resulting in AUROC of 0.904. In test set, AUROC was reported at 0.775 [0.5216, 1] with PPV = NPV = 71.42%. Table 6. Number of samples per POP with KRAS mutations. GeneName POP-NR.M POP-NR.WT POP-R.M POP-R.WT Fishers.pval ABCA7 0 24 4 18 0044826

Example 2: Differential gene expression between CAP vs CFP samples (Table 2) Gene Name log2 Fold Fold pval padj t.pval DE

Attorney Docket No.07039-2155WO1 / 2022-250 SOX11 5.319 39.914 1.08E-17 3.77E-14 1.02E-08 Up SFRP2 4.748 26.872 2.37E-17 6.45E-14 2.33E-08 Up

Attorney Docket No.07039-2155WO1 / 2022-250 LINC01234 4.068 16.77 2.33E-12 1.04E-09 6.81E-06 Up CD248 1.752 3.368 2.55E-12 1.11E-09 5.61E-08 Up

Attorney Docket No.07039-2155WO1 / 2022-250 C3 1.724 3.304 6.10E-11 1.46E-08 5.73E-06 Up UGT1A4 -1.266 0.416 6.38E-11 1.51E-08 8.66E-07 Down

Attorney Docket No.07039-2155WO1 / 2022-250 TGM2 1.25 2.379 3.93E-10 6.40E-08 7.03E-07 Up MFAP2 1.26 2.395 4.04E-10 6.52E-08 5.84E-08 Up

Attorney Docket No.07039-2155WO1 / 2022-250 ENOX1 1.117 2.169 1.86E-09 2.28E-07 1.37E-07 Up HMCN1 1.172 2.253 1.99E-09 2.43E-07 1.55E-06 Up

Attorney Docket No.07039-2155WO1 / 2022-250 AC107983.4 -1.521 0.348 6.63E-09 6.48E-07 2.06E-06 Down RP11-169F17.1 4.22 18.638 6.82E-09 6.62E-07 0.003683 Up

Attorney Docket No.07039-2155WO1 / 2022-250 AC132217.4 2.052 4.148 2.48E-08 1.98E-06 0.000196 Up RP11-627K11.1 -1.18 0.441 2.69E-08 2.14E-06 2.26E-05 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ETV1 1.071 2.1 1.12E-07 7.35E-06 7.17E-06 Up RP5-1024G6.8 1.034 2.048 1.16E-07 7.53E-06 1.58E-05 Up

Attorney Docket No.07039-2155WO1 / 2022-250 RP11-519G16.5 -1.117 0.461 2.40E-07 1.34E-05 0.000125 Down KCNJ8 1.163 2.24 2.43E-07 1.34E-05 4.51E-05 Up

Attorney Docket No.07039-2155WO1 / 2022-250 RP11-693N9.2 -1.158 0.448 4.61E-07 2.24E-05 5.79E-05 Down ENPEP 1.032 2.045 4.66E-07 2.25E-05 5.90E-05 Up

Attorney Docket No.07039-2155WO1 / 2022-250 HBEGF 1.324 2.503 1.08E-06 4.59E-05 0.007047 Up CWH43 -1.663 0.316 1.09E-06 4.63E-05 0.000271 Down

Attorney Docket No.07039-2155WO1 / 2022-250 SPEG 1.005 2.007 2.69E-06 9.76E-05 0.000322 Up LUM 1.223 2.334 2.75E-06 9.97E-05 0.000307 Up

Attorney Docket No.07039-2155WO1 / 2022-250 RPS3AP25 -1.033 0.489 6.01E-06 0.000188 0.000201 Down OR51E1 1.325 2.505 6.17E-06 0.000192 0.007294 Up

Attorney Docket No.07039-2155WO1 / 2022-250 FEZF1-AS1 1.697 3.243 1.56E-05 0.000404 0.000677 Up MUC17 1.726 3.308 1.57E-05 0.000404 0.01799 Up

Attorney Docket No.07039-2155WO1 / 2022-250 TREM1 1.567 2.963 3.05E-05 0.000694 7.89E-05 Up BST2 1.035 2.049 3.07E-05 0.000696 0.000862 Up

Attorney Docket No.07039-2155WO1 / 2022-250 LINC01436 1.599 3.029 6.42E-05 0.001253 0.0036 Up MIR200B -1.052 0.482 6.47E-05 0.00126 0.005109 Down

Attorney Docket No.07039-2155WO1 / 2022-250 SLC6A19 1.792 3.462 0.000135 0.002282 0.024897 Up MIR23B -1.018 0.494 0.000141 0.002364 0.009155 Down

Attorney Docket No.07039-2155WO1 / 2022-250 PRODH 1.441 2.715 0.000296 0.004124 0.014507 Up IL21R-AS1 1.261 2.397 0.000298 0.004144 0.00558 Up

Attorney Docket No.07039-2155WO1 / 2022-250 PLA2G12B 1.395 2.629 0.000845 0.009434 0.013925 Up CPS1 1.524 2.876 0.000852 0.009492 0.078066 Up

Attorney Docket No.07039-2155WO1 / 2022-250 C10orf55 1.004 2.006 0.001816 0.016923 0.018401 Up FEZF1 1.37 2.584 0.001835 0.017033 0.010419 Up

Attorney Docket No.07039-2155WO1 / 2022-250 GABRB2 -1.192 0.438 0.00697 0.046791 0.01361 Down RP11-67L14.1 1.008 2.011 0.007198 0.04797 0.073011 Up

Example 3: Differential gene expression between POP-NR and POP-R (Table 5) Gene Name log2 Fold Fold pval padj t.pval DE Change change

Attorney Docket No.07039-2155WO1 / 2022-250 Example 4: KRAS COSMIC details (Table 7) POP COSMIC_v92_GRCh38.SAMPLE. Sample ID status Chr Position Ref Alt MUTATION_ID

Attorney Docket No.07039-2155WO1 / 2022-250 95610753 B91_10010062 POP.NR 12 25245328 C A c.57G>T_p.Leu19Phe

Example 5: Differentially expressed genes in POP-R category between KRAS mutant and KRAS wild-type cases (Table 8) log2 Fold Fold GeneId Gene Name Change change pval padj t.pval DE

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000133134 BEX2 -2.252 0.21 5.83E-07 0.0007592 0.000111 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000163359 COL6A3 -1.418 0.374 3.08E-06 0.0017548 0.0005519 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000130413 STK33 -1.981 0.253 1.18E-05 0.004289 0.0005506 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000151650 VENTX -2.064 0.239 1.89E-05 0.0049672 0.0510965 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000019186 CYP24A1 2.427 5.377 3.65E-05 7.77E-03 1.19E-03 Up

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000152785 BMP3 -2.417 0.187 7.17E-05 0.0125844 0.0258924 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000211947 IGHV3-21 -1.619 0.326 9.78E-05 0.0148153 0.0324427 Down

Attorney Docket No.07039-2155WO1 / 2022-250 0.000140 ENSG00000182636 NDN -1.163 0.447 3 0.0183096 2.00E-05 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000067715 SYT1 2.321 4.997 1.90E-04 0.0208354 0.0069216 Up

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000110911 SLC11A2 1.051 2.072 2.51E-04 0.0249102 0.0022792 Up

Attorney Docket No.07039-2155WO1 / 2022-250 0.000309 ENSG00000221866 PLXNA4 -1.552 0.341 8 0.0280066 0.0042691 Down

Attorney Docket No.07039-2155WO1 / 2022-250 RP11- 0.000371 ENSG00000257176 996F15.2 1.041 2.057 7 0.0307004 0.0022551 Up

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000124772 CPNE5 -1.194 0.437 4.84E-04 0.036783 0.0143832 Down

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000105369 CD79A -1.513 0.35 5.86E-04 0.0398531 0.0187365 Down

Attorney Docket No.07039-2155WO1 / 2022-250 0.000657 ENSG00000211957 IGHV3-35 -1.414 0.375 1 0.0420672 0.0049759 Down

Attorney Docket No.07039-2155WO1 / 2022-250 0.000820 ENSG00000172935 MRGPRF -1.341 0.395 6 0.048411 0.0001881 Down

cases (Table 9) log2 F ld F ld

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000197614 MFAP5 2.614 6.121 3.49E-09 7.61E-06 0.000192 Up ENSG00000102109 PCSK1N 3.782 13.753 4.88E-09 9.66E-06 0.019058 Up

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000136732 GYPC 1.406 2.65 1.25E-06 0.000504 8.99E-05 Up ENSG00000161249 DMKN 1.775 3.421 1.22E-06 0.000504 6.36E-05 Up n n

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000100033 PRODH 3.144 8.841 1.32E-05 0.003087 0.059056 Up ENSG00000182272 B4GALNT4 1.936 3.827 1.33E-05 0.003087 0.018997 Up n n

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000133083 DCLK1 1.51 2.848 4.76E-05 0.007421 0.001557 Up ENSG00000157514 TSC22D3 1.129 2.188 4.80E-05 0.007421 0.001922 Up n n n n n

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000168497 SDPR 1.053 2.074 0.000104 0.012253 0.000517 Up IGHV1OR15- n n n n n n

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000187955 COL14A1 1.074 2.105 0.000198 0.018957 0.001462 Up ENSG00000171867 PRNP 1.003 2.005 0.0002 0.019009 0.010452 Up n n n n n

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000211611 IGKV6-21 2.04 4.112 0.000303 0.024511 0.009401 Up ENSG00000226278 PSPHP1 -6.719 0.009 0.000304 0.024511 0.184573 Down n

Attorney Docket No.07039-2155WO1 / 2022-250 CTD- ENSG00000267042 3193K9.4 1.879 3.677 0.000436 0.029699 0.068855 Up n n n n n n n n n

Attorney Docket No.07039-2155WO1 / 2022-250 ENSG00000132185 FCRLA 1.914 3.769 0.000716 0.041744 0.006305 Up ENSG00000163534 FCRL1 1.75 3.364 0.000716 0.041744 0.061373 Up n n

Attorney Docket No.07039-2155WO1 / 2022-250 Example 7: Predicting Spatial Colorectal Polyp Recurrence This Example identifies markers that are unique to POP-CRC as compared to both POP-R (recurrent polyps) and POP-NR (non-recurrent polyps). SSA-TSA polyps The expression of specific markers was evaluated in specific cellular compartments (epithelial compartments or stromal compartments) in a sessile serrated adenoma (SSA) or a traditional serrated adenoma (TSA) that was cancer free when it was first removed (Figure 12). a) Epithelium compartment specific: 1) CTNND2 upregulated (raw P < 0.05) 2) LIPE upregulated (raw P < 0.05) 3) MT2A downregulated (raw P < 0.05) 4) MZT2B upregulated (FDR < 0.001) 5) H4C5 downregulated (raw P < 0.05) 6) MT1E downregulated (raw P < 0.05) b) Stroma specific: 1) IGLL5 downregulated (raw P < 0.05) 2) COX6B1 downregulated (raw P < 0.05) 3) GNAI2 downregulated (raw P < 0.05) 4) KRT8 downregulated (raw P < 0.05) 5) MYH9 downregulated (raw P < 0.05) 6) TPM4 downregulated (raw P < 0.05) 7) TAGLN2 downregulated (raw P < 0.05) 8) OAZ1 downregulated (raw P < 0.05) 9) LAPTM5 downregulated (raw P < 0.05) 10) CCNI downregulated (raw P < 0.05) 11) ATP5ME downregulated (raw P < 0.05) 12) HSP90AB1 downregulated (raw P < 0.05) 13) MZB1 downregulated (raw P < 0.05) 14) LENG8 downregulated (raw P < 0.05) 15) MYL6 downregulated (raw P < 0.05) 16) ALDOA downregulated (raw P < 0.05) 17) H1-5 downregulated (raw P < 0.05) 18) RPS11 downregulated (raw P < 0.05) 19) IGHG2, IGHG3, IGHG4, IGHM downregulated (raw P < 0.05) Attorney Docket No.07039-2155WO1 / 2022-250 POP-R markers identified in SSA-TSA polyps were as follows: a) Epithelium specific None b) Stroma specific None TA-TV-VA polyps The expression of specific markers was evaluated in specific cellular compartments (epithelial compartments or stromal compartments) in a tubular adenoma (TA), tubulovillous (TV), or villous adenoma (VA) that was cancer free when it was first removed (Figure 13). a) Epithelium specific 1) PHGR1 downregulated (raw P < 0.05) 2) IGLL5 downregulated (raw P < 0.05) 3) FABP1 downregulated (raw P < 0.05) b) Stroma specific 1) IGLL5 downregulated (raw P < 0.05) 2) PIGR downregulated (raw P < 0.05) POP-R markers identified in TA-TV-VA polyps were as follows: a) Epithelium specific 1) ATP5MC2 upregulated (raw P < 0.05) 2) IGLL5 downregulated (raw P < 0.05) 3) TFF1 downregulated (raw P < 0.05) 4) IGHM downregulated (raw P < 0.05) b) Stroma specific 1) MZT2B upregulated (raw P < 0.05) 2) MUC2 downregulated (raw P < 0.05) 3) KRT20 downregulated (raw P < 0.05) 4) REG4 downregulated (FDR < 0.05) 5) TFF1 (FDR < 0.05) Attorney Docket No.07039-2155WO1 / 2022-250 The presence of the specific markers assessed (e.g., specific genes whose expression was either up regulated or down regulated) can predict that upon a follow up colonoscopy, cancer will develop in the same place from which the original polyp was removed (Figure 14). For example, IGLL5 was downregulated in POP-CRC SSA-TSA and TA-TV-VA polyps, and the presence of a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide) can be used to identify a polyp as being likely to become malignant. Example 8: Assessing Colon Polyps A tissue sample containing one or more polyp cells is obtained from a human having one or more colon polyps. The obtained sample is examined for the presence or absence of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content. If the sample includes the presence of one or more of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more changes in genetic content (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content), then the polyp is classified as being or likely to become malignant. If the sample lacks an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more changes in genetic content (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content), then the polyp is classified as not being or not likely to become malignant. Example 9: Treating Colon Polyps A tissue sample containing one or more polyp cells is obtained from a human having one or more colon polyps. The obtained sample is examined for the presence or absence of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more changes in genetic content (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content). If the sample includes the presence of one or more of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more changes in genetic content (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content), then the human is subjected to one or more colon polyp treatments (e.g., surgery to remove the polyp(s)) and one or more cancer treatments. The treatment can reduce number of polyps within the human while minimizing the risk of metastasis. Example 10: Treating Colon Polyps A tissue sample containing one or more polyp cells is obtained from a human having one or more colon polyps. The obtained sample is examined for the presence or absence of an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a Attorney Docket No.07039-2155WO1 / 2022-250 SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more changes in genetic content (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content). If the sample lacks an increased level of an ADAMTS4 polypeptide (or mRNA encoding an ADAMTS4 polypeptide), an increased level of a THBS2 polypeptide (or mRNA encoding a THBS2 polypeptide), an increased level of a SERPINE1 polypeptide (or mRNA encoding a SERPINE1 polypeptide), an increased level of a FAP polypeptide (or mRNA encoding a FAP polypeptide), an increased level of a CYR61 polypeptide (or mRNA encoding a CYR61 polypeptide), an increased level of a SOX11 polypeptide (or mRNA encoding a SOX11 polypeptide), an increased level of a CXCL13 polypeptide (or mRNA encoding a CXCL13 polypeptide), an increased level of a SFRP2 polypeptide (or mRNA encoding a SFRP2 polypeptide), an increased level of a VIP polypeptide (or mRNA encoding a VIP polypeptide), an increased level of a TERT polypeptide (or mRNA encoding a TERT polypeptide), an increased numbers of NKCs in the resting phase, and one or more changes in genetic content (e.g., an increased frequency of genomic DUPs, an increased frequency of genomic DELs, an increased frequency of LOH, and a higher telomere content), then the human is subjected to one or more colon polyp treatments to remove the polyp(s) (e.g., colonoscopic polypectomy). The surgery can reduce number of polyps within the human while sparing the human from unnecessary risks and/or complications associated with cancer treatment(s). Example 11: Assessing Colon Polyps A tissue sample containing one or more polyp cells is obtained from a human having one or more colon polyps. The obtained sample is examined for the presence or absence of Attorney Docket No.07039-2155WO1 / 2022-250 an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH). If the sample includes the presence of one or more of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH), then the polyp is classified as being likely to recur. If the sample (a) lacks an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH), and (b) contains Attorney Docket No.07039-2155WO1 / 2022-250 a wild type KRAS polypeptide (or a nucleic acid encoding a wild type KRAS polypeptide), then the polyp is classified as not being likely to recur. Example 12: Treating Colon Polyps A tissue sample containing one or more polyp cells is obtained from a human having one or more colon polyps. The obtained sample is examined for the presence or absence of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH). If the sample includes the presence of one or more of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH), then the human is subjected to one or more colon polyp treatments (e.g., surgery to remove the polyp(s)) and one or more additional polyp treatments. The treatment can reduce number of polyps within the human while minimizing the risk of recurrence. Attorney Docket No.07039-2155WO1 / 2022-250 Example 13: Treating Colon Polyps A tissue sample containing one or more polyp cells is obtained from a human having one or more colon polyps. The obtained sample is examined for the presence or absence of an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), one or more mutations in a KRAS polypeptide (or a nucleic acid encoding a KRAS polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH). If the sample lacks (a) an increased level of a TPRG1 polypeptide (or mRNA encoding a TPRG1 polypeptide), an increased level of an LY6G6C polypeptide (or mRNA encoding an LY6G6C polypeptide), an increased level of a DUSP4 polypeptide (or mRNA encoding a DUSP4 polypeptide), an increased level of a ZIC5 polypeptide (or mRNA encoding a ZIC5 polypeptide), an increased level of a CYP1A1 polypeptide (or mRNA encoding a CYP1A1 polypeptide), an increased level of a DMKN polypeptide (or mRNA encoding a DMKN polypeptide), and a decreased level of an IGLL5 polypeptide (or mRNA encoding an IGLL5 polypeptide), and one or more changes in genetic content (e.g., an increased frequency of genomic DELs and an increased frequency of LOH), and (b) contains a wild type KRAS polypeptide (or a nucleic acid encoding a wild type KRAS polypeptide), then the human is subjected to one or more colon polyp treatments (e.g., surgery to remove the polyp(s)). The surgery can reduce number of polyps within the human while sparing the human from unnecessary risks and/or complications associated with additional polyp treatments. OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not Attorney Docket No.07039-2155WO1 / 2022-250 limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.07039-2155WO1 / 2022-250 W^HAT I^S C^LAIMED I^S: 1. A method for assessing a mammal having one or more colon polyps, wherein said method comprises: (a) determining (i) if a sample from said mammal contains the presence or absence of at least one of (1) an increased level of a TERT polypeptide or mRNA encoding said TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide, and (ii) if said sample contains the presence or absence of at least one of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of natural killer cells (NKCs) in the resting phase, (12) an increased frequency of genomic duplications (DUPs), (13) an increased frequency of genomic deletions (DELs), (14) an increased frequency of loss of heterozygosity (LOH), and (15) a higher telomere content; (b) classifying said colon polyps as being malignant if said presence of at least one of (1)-(4) is determined and said presence of at least one of (5)-(15) is determined; and (c) classifying said colon polyps as not being malignant if said absence of each of (1)- (15) is determined. 2. The method of claim 1, wherein said mammal is a human. 3. The method of any one of claims 1-2, wherein said presence or absence of said increased level of said TERT polypeptide or mRNA encoding said TERT polypeptide is determined. Attorney Docket No.07039-2155WO1 / 2022-250 4. The method of any one of claims 1-2, wherein said presence or absence of said increased level of said FAP polypeptide or mRNA encoding said FAP polypeptide is determined. 5. The method of any one of claims 1-2, wherein said presence or absence of said increased level of said SOX11 polypeptide or mRNA encoding said SOX11 polypeptide is determined. 6. The method of any one of claims 1-2, wherein said presence or absence of said increased level of said CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide is determined. 7. The method of any one of claims 1-2, wherein said method comprises determining the presence of each of said (1)-(4). 8. The method of any one of claims 1-2, wherein said method comprises determining the presence of each of said (1)-(15). 9. The method of any one of claims 7-8, wherein said method comprises classifying said colon polyps as being malignant. 10. The method of any one of claims 1-2, wherein said method comprises determining the absence of each of said (1)-(15). 11. The method of claim 10, wherein said method comprises classifying said colon polyps as not being malignant. 12. The method of any one of claims 1-11, wherein said sample is a tissue sample comprising one or more polyp cells. Attorney Docket No.07039-2155WO1 / 2022-250 13. A method for assessing a mammal having one or more colon polyps, wherein said method comprises: (a) determining (i) if a sample from said mammal contains the presence or absence of at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, and (ii) if said sample contains the presence or absence of at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH; (b) classifying said colon polyps as being likely to recur if said presence of at least one of said (1)-(5) is determined and at least one of said (6)-(7) is determined; and (c) classifying said colon polyps as not being likely to recur if said absence of each of said (1)-(7) is determined. 14. The method of claim 13, wherein said mammal is a human. 15. The method of any one of claims 13-14, wherein said presence or absence of said increased level of said TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide is determined. 16. The method of any one of claims 13-14, wherein said presence or absence of said increased level of said LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide is determined. 17. The method of any one of claims 13-14, wherein said presence or absence of said increased level of said DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide is determined. Attorney Docket No.07039-2155WO1 / 2022-250 18. The method of any one of claims 13-14, wherein said presence or absence of said increased level of said CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide is determined. 19. The method of any one of claims 13-14, wherein said presence or absence of said increased level of said DMKN polypeptide or mRNA encoding said DMKN polypeptide is determined. 20. The method of any one of claims 13-14, wherein said method comprises determining the presence of each of said (1)-(5). 21. The method of any one of claims 13-14, wherein said method comprises determining the presence of each of said (1)-(9). 22. The method of claim 21, wherein said method comprises classifying said colon polyps as being likely to recur. 23. The method of any one of claims 13-14, wherein said method comprises determining the absence of each of said (1)-(9). 24. The method of claim 23, wherein said method comprises classifying said colon polyps as not being likely to recur. 25. The method of any one of claims 13-24, wherein said sample is a tissue sample comprising one or more polyp cells. 26. A method for selecting a treatment for a mammal having one or more colon polyps, wherein said method comprises: (a) determining (i) that a sample from said mammal contains the presence of at least one of (1) an increased level of a TERT polypeptide or mRNA encoding said TERT Attorney Docket No.07039-2155WO1 / 2022-250 polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide, and (ii) that said sample contains the presence of at least one of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content, wherein said sample is a tissue sample comprising one or more polyp cells; and (b) selecting said mammal for surgery to remove the polyps and a cancer treatment. 27. The method of claim 26, wherein said mammal is a human. 28. The method of any one of claims 26-27, wherein said surgery to remove the polyps comprises a polypectomy. 29. The method of any one of claims 26-28, wherein said cancer treatment comprises radiation therapy. 30. The method of any one of claims 26-28, wherein said cancer treatment comprises administering an anti-cancer drug to said mammal. 31. The method of claim 30, wherein said anti-cancer drug is selected from the group consisting of docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, and combinations thereof. Attorney Docket No.07039-2155WO1 / 2022-250 32. A method for selecting a treatment for a mammal having one or more colon polyps, wherein said method comprises: (a) determining that a sample from said mammal contains the absence of (1) an increased level of a TERT polypeptide or mRNA encoding said TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide, (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content, wherein said sample is a tissue sample comprising one or more polyp cells; and (b) selecting said mammal for a colon polyp treatment in the absence of a cancer treatment. 33. The method of claim 32, wherein said mammal is a human. 34. The method of any one of claims 32-33, wherein said colon polyp treatment comprises surgery to remove the polyps. 35. The method of any one of claims 32-34, wherein said cancer treatment comprises radiation therapy. 36. The method of any one of claims 32-34, wherein said cancer treatment comprises administering an anti-cancer drug to said mammal. Attorney Docket No.07039-2155WO1 / 2022-250 37. The method of claim 36, wherein said anti-cancer drug is selected form the group consisting of docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, and combinations thereof. 38. A method for selecting a treatment for a mammal having one or more colon polyps, wherein said method comprises: (a) determining (i) that a sample from said mammal contains the presence of at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, and (ii) that said sample contains the presence of at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH, wherein said sample is a tissue sample comprising one or more polyp cells; and (b) selecting said mammal for colonoscopic polypectomy to remove the polyps. 39. The method of claim 38, wherein said mammal is a human. 40. A method for selecting a treatment for a mammal having one or more colon polyps, wherein said method comprises: (a) determining that a sample from said mammal contains the absence of (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, Attorney Docket No.07039-2155WO1 / 2022-250 (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH, wherein said sample is a tissue sample comprising one or more polyp cells; and (b) selecting said mammal for a colon polyp treatment, wherein said colon polyp treatment does not include any surgery to remove the polyps. 41. The method of claim 40, wherein said mammal is a human. 42. A method for treating a mammal having one or more colon polyps, wherein said method comprises: (a) determining (i) that a sample from said mammal comprises one or more of (1) an increased level of a TERT polypeptide or mRNA encoding said TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide and (ii) that said sample comprises one or more of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content; (b) subjecting said mammal to surgery to remove the polyps; and (c) administering a cancer treatment to said mammal. Attorney Docket No.07039-2155WO1 / 2022-250 43. A method for treating colon polyps, wherein said method comprises subjecting a mammal identified as comprising a sample (i) comprising one or more of (1) an increased level of a TERT polypeptide or mRNA encoding said TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, and (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide, and (ii) comprising one or more of (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content to a surgery to remove the polyps, and administering a cancer treatment to said mammal. 44. The method of any one of claims 42-43, wherein said mammal is a human. 45. The method of any one of claims 42-44, wherein said sample is a tissue sample comprising one or more polyp cells. 46. The method of any one of claims 42-45, wherein said surgery to remove the polyps comprises a polypectomy. 47. The method of any one of claims 42-46, wherein said cancer treatment comprises radiation therapy. 48. The method of any one of claims 42-46, wherein said cancer treatment comprises administering an anti-cancer drug to said mammal. Attorney Docket No.07039-2155WO1 / 2022-250 49. The method of claim 48, wherein said anti-cancer drug is selected from the group consisting of docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, and combinations thereof. 50. A method for treating a mammal having one or more colon polyps, wherein said method comprises: (a) determining that a sample from said mammal lacks (1) an increased level of a TERT polypeptide or mRNA encoding said TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide, (5) an increased level of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of NKC in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content; and (b) administering a colon polyp treatment to said mammal in the absence of a cancer treatment. 51. A method for treating colon polyps, wherein said method comprises subjecting a mammal identified as comprising a sample lacking (1) an increased level of a TERT polypeptide or mRNA encoding said TERT polypeptide, (2) an increased level of a FAP polypeptide or mRNA encoding said FAP polypeptide, (3) an increased level of a SOX11 polypeptide or mRNA encoding said SOX11 polypeptide, (4) an increased level of a CXCL13 polypeptide or mRNA encoding said CXCL13 polypeptide, (5) an increased level Attorney Docket No.07039-2155WO1 / 2022-250 of an ADAMTS4 polypeptide or mRNA encoding said ADAMTS4 polypeptide, (6) an increased level of a THBS2 polypeptide or mRNA encoding said THBS2 polypeptide, (7) an increased level of a SERPINE1 polypeptide or mRNA encoding said SERPINE1 polypeptide, (8) an increased level of a CYR61 polypeptide or mRNA encoding said CYR61 polypeptide, (9) an increased level of a SFRP2 polypeptide or mRNA encoding said SFRP2 polypeptide, (10) an increased level of a VIP polypeptide or mRNA encoding said VIP polypeptide, (11) an increased numbers of NKCs in the resting phase, (12) an increased frequency of genomic DUPs, (13) an increased frequency of genomic DELs, (14) an increased frequency of LOH, and (15) a higher telomere content to a colon polyp treatment to said mammal in the absence of a cancer treatment. 52. The method of any one of claims 50-51, wherein said mammal is a human. 53. The method of any one of claims 50-52, wherein said sample is a tissue sample comprising one or more polyp cells. 54. The method of any one of claims 50-53, wherein said colon polyp treatment comprises surgery to remove the polyps. 55. The method of any one of claims 50-54, wherein said cancer treatment comprises radiation therapy. 56. The method of any one of claims 50-54, wherein said cancer treatment comprises administering an anti-cancer drug to said mammal. 57. The method of claim 56, wherein said anti-cancer drug is selected from the group consisting of docetaxel, capecitabine, cyclophosphamide, epirubicin, fluorouracil, bevacizumab, cetuximab, panitumumab, ramucirumab, regorafenib, ziv-aflibercept, and combinations thereof. Attorney Docket No.07039-2155WO1 / 2022-250 58. A method for treating a mammal having one or more colon polyps, wherein said method comprises: (a) determining (i) that a sample from said mammal comprises at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, and (ii) that said sample comprises at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH; and (b) subjecting said mammal to colonoscopic polypectomy to remove the polyps. 59. A method for treating colon polyps, wherein said method comprises subjecting a mammal identified as comprising a sample (i) comprising at least one of (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, and (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, and (ii) comprising at least one of (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH to surgery to remove the polyps. 60. The method of any one of claims 58-59, wherein said mammal is a human. 61. The method of any one of claims 58-60, wherein said sample is a tissue sample comprising one or more polyp cells. Attorney Docket No.07039-2155WO1 / 2022-250 62. A method for treating a mammal having one or more colon polyps, wherein said method comprises: (a) determining that a sample from said mammal contains the absence of (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH, wherein said sample is a tissue sample comprising one or more polyp cells; and (b) selecting said mammal for a colon polyp treatment, wherein said colon polyp treatment does not include any surgery to remove the polyps. 63. A method for treating colon polyps, wherein said method comprises subjecting a mammal identified as comprising a sample lacking (1) an increased level of a TPRG1 polypeptide or mRNA encoding said TPRG1 polypeptide, (2) an increased level of a LY6G6C polypeptide or mRNA encoding said LY6G6C polypeptide, (3) an increased level of a DUSP4 polypeptide or mRNA encoding said DUSP4 polypeptide, (4) an increased level of a CYP1A1 polypeptide or mRNA encoding said CYP1A1 polypeptide, (5) an increased level of a DMKN polypeptide or mRNA encoding said DMKN polypeptide, (6) an increased level of a ZIC5 polypeptide or mRNA encoding said ZIC5 polypeptide, (7) one or more mutations in a KRAS polypeptide or a nucleic acid encoding a KRAS polypeptide, (8) an increased frequency of genomic DELs, and (9) an increased frequency of LOH to a colon polyp treatment, wherein said colon polyp treatment does not include any surgery to remove the polyps. 64. The method of any one of claims 62-63, wherein said mammal is a human. Attorney Docket No.07039-2155WO1 / 2022-250 65. The method of any one of claims 62-64, wherein said sample is a tissue sample comprising one or more polyp cells. 66. A method performed by one or more computers, wherein said method comprises: (a) receiving a set of features characterizing a mammal, wherein said mammal has one or more colon polyps, and wherein said set of features comprises one or more transcriptomic features of said mammal; (b) processing said set of features characterizing said mammal using a polyp prediction machine learning model, in accordance with values of a set of machine learning model parameters, to generate a machine learning model output, wherein the machine learning model output defines one or more predictions characterizing said one or more colon polyps of said mammal; and generating a notification that indicates said one or more predictions characterizing said one or more colon polyps of said mammal. 67. The method of claim 66, wherein said machine learning model output comprises a likelihood that said one or more colon polyps are malignant. 68. The method of any one of claims 66-67, wherein said machine learning model output comprises a likelihood that said one or more colon polyps will recur. 69. The method of any one of claims 66-68, wherein said set of features characterizing said mammal are derived from a sample obtained from said mammal. 70. The method of any one of claims 66-69, wherein said set of features characterizing said mammal comprises transcriptomic features. 71. The method of claim 70, wherein said transcriptomic features comprise normalized values of one or more protein coding genes in said mammal. Attorney Docket No.07039-2155WO1 / 2022-250 72. The method of claim 71, wherein said transcriptomic features comprise normalized values of one or more of: ADAMTS4 genes, THBS2 genes, SERPINE1 genes, FAP genes, CYR61 genes, SOX11 genes, CXCL13 genes, SFRP2 genes, VIP genes, or TERT genes. 73. The method of any one of claims 66-72, wherein said set of features characterizing said mammal include one or more of: genomic features, epigenomic features, proteomic features, or metabolomic features. 74. The method of any one of claims 66-73, wherein said polyp prediction machine learning model comprises one or more of: a linear regression model, a random forest model, a support vector machine model, a neural network model, or an XGBoost model. 75. The method of any one of claims 66-74, wherein said polyp prediction machine learning model have been trained by operations comprising: (a) obtaining a set of training examples, wherein each training example comprises: (i) a set of training features characterizing a training mammal having one or more colon polyps, and (ii) a target output characterizing the one or more colon polyps of the mammal; and (b) training said set of machine learning model parameters of said polyp prediction machine learning model on said set of training examples, comprising, for each training example: (i) training said polyp prediction machine learning model to process said set of training features from said training example to generate a machine learning model output that matches the target output from the training example. 76. The method of any one of claims 66-75, further comprising taking an action based on said one or more predictions characterizing said one or more colon polyps of said mammal. 77. The method of claim 76, wherein said action comprises increasing a rate of screening for said one or more colon polyps of said mammal. Attorney Docket No.07039-2155WO1 / 2022-250 78. The method of any one of claims 76-77, wherein said action comprises removing said one or more colon polyps of said mammal. 79. The method of any one of claims 66-78, further comprising generating a set of explainability data that explains said one or more predictions generated by said polyp prediction machine learning model, comprising: (a) generating, for each feature in said set of features characterizing said mammal, an impact score that characterizes an impact of said feature on said one or more predictions generated by said polyp prediction machine learning model for said one or more colon polyps of said mammal. 80. The method of claim 79, further comprising: (a) identifying one or more features having the highest impact scores from among said set of features; and (b) generating a notification that indicates said one or more features having the highest impact scores from among said set of features. 81. A system comprising: (a) one or more computers; and (b) one or more storage devices communicatively coupled to said one or more computers, wherein said one or more storage devices store instructions that, when executed by said one or more computers, cause said one or more computers to perform operations of the respective method of any one of claims 66-80. 82. One or more non-transitory computer storage media storing instructions that when executed by one or more computers cause the one or more computers to perform operations of the respective method of any one of claims 66-80. 83. The method of claim 13, said method further comprising determining that said sample contains the presence or absence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. Attorney Docket No.07039-2155WO1 / 2022-250 84. The method of claim 83, said method further comprising classifying said colon polyps as being likely to recur if said presence of said decreased level of said IGLL5 polypeptide or said decreased level of said mRNA encoding said IGLL5 polypeptide is determined. 85. The method of claim 83, said method further comprising classifying said colon polyps as not being likely to recur if said absence of said decreased level of said IGLL5 polypeptide or said decreased level of said mRNA encoding said IGLL5 polypeptide is determined. 86. The method of claim 38, said method further comprising determining that said sample contains the presence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. 87. The method of claim 40, said method further comprising determining that said sample from said mammal contains the absence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. 88. The method of claim 58, said method further comprising determining that said sample comprises a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. 89. The method of claim 59, wherein said sample further comprises a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. 90. The method of claim 62, said method further comprising determining that said sample contains the absence of a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide. Attorney Docket No.07039-2155WO1 / 2022-250 91. The method of claim 63, wherein said sample further lacks a decreased level of an IGLL5 polypeptide or a decreased level of an mRNA encoding said IGLL5 polypeptide.