ArticleCancer research2010
Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 115 citations in OpenAlex.
- Hereditary Endometrial Cancer: Lynch Syndrome, Mismatch Repair Deficiency, and Emerging Genetic Predispositions-A Comprehensive Review with Clinical and Laboratory Guidelines.International journal of molecular sciences · 2026Review
- MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.Acta neuropathologica · 2025Article
- High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.World journal of oncology · 2024Article
- Article
- Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas.Scientific reports · 2023Article
- Expression differences between proteins responsible for DNA damage repair according to the Gleason grade as a new heterogeneity marker in prostate cancer.Archives of medical science : AMS · 2023Article
- Review
- Morphologic and Genomic Characteristics of Breast Cancers Occurring in Individuals with Lynch Syndrome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Clonal relationship and directionality of progression of synchronous endometrial and ovarian carcinomas in patients with DNA mismatch repair-deficiency associated syndromes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Promoter hypomethylation as potential confounder of Ras gene overexpression and their clinical significance in subsets of urothelial carcinoma of bladder.Molecular biology reports · 2021Article
- Detection ofJournal of oncology · 2021Article
- Intratumor Epigenetic Heterogeneity-A Panel Gene Methylation Study in Thyroid Cancer.Frontiers in genetics · 2021Article
- Complete Loss of EPCAM Immunoexpression IdentifiesCancers · 2020Article
- Epigenetic based synthetic lethal strategies in human cancers.Biomarker research · 2020Review
- EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome.Human mutation · 2019Article
- Epigenetic heterogeneity in cancer.Biomarker research · 2019Review
- Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs.Medicina oral, patologia oral y cirugia bucal · 2018Article
- Drugging the Cancers Addicted to DNA Repair.Journal of the National Cancer Institute · 2017Review
- Association of a novel point mutation in MSH2 gene with familial multiple primary cancers.Journal of hematology & oncology · 2017Article
- Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: implications for immunotherapy.Oncotarget · 2017Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Heritable germline epimutations in MSH2 have been reported in a few Lynch syndrome families that lacked germline mutations in the MSH2 gene. It is not known whether somatic MSH2 methylation occurs in MSH2 mutation-positive Lynch syndrome subjects or sporadic colorectal cancers (CRC). Therefore, we determined the methylation status of the MSH2 gene in 268 CRC tissues, including 222 sporadic CRCs and 46 Lynch syndrome tumors that did not express MSH2. We also looked for microsatellite instability (MSI), germline mutations in the MSH2 and EpCAM genes, somatic mutations in BRAF and KRAS, and the CpG island methylator phenotype (CIMP). We observed that somatic MSH2 hypermethylation was present in 24% (11 of 46) of MSH2-deficient (presumed Lynch syndrome) tumors, whereas no evidence for MSH2 methylation existed in sporadic CRCs (MSI and microsatellite stable) or normal colonic tissues. Seven of 11 (63%) patients with MSH2 methylation harbored simultaneous pathogenic germline mutations in the MSH2 gene. Germline EpCAM deletions were present in three of four patients with MSH2 methylation but without pathogenic MSH2 germline mutations. The mean methylation scores at CIMP-related markers were significantly higher in Lynch syndrome tumors with MSH2 methylation than MSH2-unmethylated CRCs. In conclusion, our data provide evidence for frequent MSH2 hypermethylation in Lynch syndrome tumors with MSH2 deficiency. MSH2 methylation in this subset of individuals is somatic and may serve as the "second hit" at the wild-type allele. High levels of aberrant methylation at CIMP-related markers in MSH2-methylated tumors raise the possibility that MSH2 is a target susceptible to aberrant methylation in Lynch syndrome.
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