Multi‐omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 12; pp. 13551 - 13572
• Main Authors: Devall, Matthew, Ali, Mourad W., Eaton, Stephen, Weisenberger, Daniel J., Reilley, Matthew J., Powell, Steven M., Li, Li, Casey, Graham
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc; Wiley
• Subjects: Biomarkers, Tumor - genetics; Biopsy; Bisulfite; Cancer; Cell Cycle Proteins - genetics; Colon; colon organoids; Colorectal cancer; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology; CRISPR; DNA methylation; DNA microarrays; DNA Mismatch Repair - genetics; Endometrium; Gene expression; Genes; Genetic disorders; Genomics; Humans; Lynch syndrome; Microsatellite Instability; Mismatch repair; MLH1 protein; MSH2 protein; MSH6 protein; Multiomics; Mutation; Organoids; Penicillin; R&D; Research & development; Surveillance; Tumors; Yeast; United States > US; colon organoids; microsatellite instability; colorectal cancer; Lynch syndrome

Introduction Lynch syndrome (LS) is a hereditary condition that increases the risk of colorectal (CRC) and extracolonic cancers that exhibit microsatellite instability (MSI‐H). MSI‐H is driven by defective mismatch repair (dMMR), and approximately 15% of nonhereditary CRCs also exhibit MSI‐H. Here,...