Somatic mutation profiles as molecular classifiers of ulcerative colitis?associated colorectal cancer

Ulcerative colitis increases colorectal cancer risk by mechanisms that remain incompletely understood. We approached this question determining the genetic and epigenetic profiles of colitis-associated carcinomas (CA-CRC). The findings were compared to Lynch syndrome (LS), a different form predisposition shares importance immunological factors in tumorigenesis. CA-CRCs (n = 27) investigated for microsatellite instability, CpG island methylator phenotype somatic mutations 999 cancer-relevant genes (“Pan-cancer” panel). A subpanel “Pan-cancer” design (578 genes) was used LS tumors 28). Mutational loads signatures stratified into three subgroups: hypermutated microsatellite-unstable (Group 1, n 1), microsatellite-stable 2, 9) nonhypermutated 3, 17). Group 1 tumor only one with MLH1 promoter hypermethylation exhibited mismatch repair deficiency-associated Signatures 21 15. 30 32 characterized whereas no prominent single signature existed 3. TP53, most common mutational target CA-CRC (16/27, 59%), similarly affected Groups 2 but DNA Wnt signaling mutated significantly more often 2. In tumors, degree hypermutability exceeded different. conclusion, (4%) 3 (63%) comply published studies, (33%) is novel. existence molecularly distinct subgroups within may guide clinical management, such as therapy options.