{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bowen MB"],"funding":["NCRR NIH HHS","Foundation for Women’s Cancer","National Cancer Institute","NCI NIH HHS","Wharton Endowment Fund","National Institutes of Health","Cancer Prevention and Research Institute of Texas"],"pagination":["e185946"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11949016"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(6)"],"pubmed_abstract":["Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes, including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC (LS-EC) remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2LoxP/LoxP, abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown. By 8 months, 58% of Msh2KO mice developed endometrial atypical hyperplasia (AH), a precancerous lesion. At 12-16 months, 50% of Msh2KO mice exhibited either AH or ECs with histologic similarities to human LS-ECs. Transcriptomic profiling of EC from Msh2KO mice revealed mitochondrial dysfunction-related pathway changes. Subsequent studies in vitro and in viv"],"journal":["JCI insight"],"pubmed_title":["Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer."],"pmcid":["PMC11949016"],"funding_grant_id":["N/A","P30CA016672","P30CA016086","CA016672","P30 CA016672","P30 CA016086","R25CA056452","Roberta Detz Endometrial Cancer Grant","S10 RR029552","R25 CA056452","R01 CA216103","R01CA216103"],"pubmed_authors":["Chan WK","Tan L","Broaddus RR","Moreno D","Lorenzi PL","Scoville DM","Peralta L","Zhang Q","Melendez B","Schmandt R","Kim TH","Lu K","Bowen MB","Jeter C","Dunner K","Zal MA","Jeong JW","Yang RK","Gokul N","Whitley E","Yates MS","Kim HE","Celestino J"],"additional_accession":[]},"is_claimable":false,"name":"Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.","description":"Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes, including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC (LS-EC) remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2LoxP/LoxP, abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown. By 8 months, 58% of Msh2KO mice developed endometrial atypical hyperplasia (AH), a precancerous lesion. At 12-16 months, 50% of Msh2KO mice exhibited either AH or ECs with histologic similarities to human LS-ECs. Transcriptomic profiling of EC from Msh2KO mice revealed mitochondrial dysfunction-related pathway changes. Subsequent studies in vitro and in viv","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-02T07:21:21.112Z","creation":"2025-07-05T03:04:43.754Z"},"accession":"S-EPMC11949016","cross_references":{"pubmed":["39964762"],"doi":["10.1172/jci.insight.185946"]}}