{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:43:57Z","timestamp":1792115037208,"version":"4.4.0"},"reference-count":92,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Colitis-associated carcinoma (CAC) represents ~1% of colorectal carcinomas and has important differences from sporadic colorectal carcinoma (sCRC). The precursors and carcinomas that arise in the setting of IBD are uniquely challenging to visualize by endoscopy and diagnose via histology, and the rising prevalence of IBD amplifies the challenges of surveillance to informed management. Although in broad strokes, CAC and sCRC share molecular features (~85% chromosomal instability pathway 15% microsatellite instability high (MSI-H)), CAC has a distinct distribution of molecular abnormalities, including lower frequencies of APC and KRAS mutations, greater prevalence of IDH1R132H, and more frequent copy number alterations (e.g., MYC amplifications), and functional data indicate that most CACs show far less dependence on Wnt signaling than sCRC, suggesting a distinct pathogenesis from the earliest stages. Although there are significant gaps in our knowledge of the pathogenesis of CAC, our understanding is growing. This review summarizes how chronic colitis reshapes epithelial homeostasis and somatic evolution, resulting in the distinctive pathogenesis of CAC, and highlights knowledge gaps that could be addressed by applying multimodal technologies to well-annotated clinical material. The review is structured in two sections, the first introducing the IBDs and the homeostatic mechanisms that preserve integrity and prevent colorectal neoplasia. The second section compares failure modes in sporadic and colitic settings and describes the differences in the resulting neoplasms.<\/jats:p>","DOI":"10.3390\/cells15050481","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:05:44Z","timestamp":1772795144000},"page":"481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Colitis-Associated Carcinoma: The Quintessential Epithelial Neoplasia Driven by Chronic Inflammation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-8268","authenticated-orcid":false,"given":"Michael G.","family":"Drage","sequence":"first","affiliation":[{"name":"Mass General Brigham, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Mino-Kenudson","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1053\/j.gastro.2021.07.042","article-title":"Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management","volume":"161","author":"Rogler","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.suc.2024.09.007","article-title":"Operative Management of Perianal Crohn\u2019s Disease","volume":"105","author":"Wilkinson","year":"2025","journal-title":"Surg. 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