ArticleInternational journal of cancer2020
Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors.
Article in International journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 162 citations in OpenAlex.
- Loss-of-Function Mutations in SWI/SNF Complexes Associated With Active Tumour Immune Microenvironment Clinical Response to Immune Checkpoint Blockade.Journal of cellular and molecular medicine · 2026Article
- Comparison of immunohistochemistry, PCR, and NGS for the evaluation of mismatch repair deficiency and microsatellite instability in colorectal cancer: a retrospective study.Diagnostic pathology · 2026Article
- Impact of germline MMR gene variants on immune checkpoint inhibitors response in patients with MSI-H/dMMR digestive cancers: a retrospective cohort analysis.Hereditary cancer in clinical practice · 2026Article
- Comprehensive Analysis of the Predictive Value of Adenylate Cyclase 4 on Clinical Significance, Prognosis, and Immunotherapy in Human Cancers.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Comparison of clinical, pathological and genomic characteristics between Lynch and non-Lynch patients with MMRd endometrial carcinoma.BMC cancer · 2026Article
- Analysis of DNA mismatch repair and microsatellite instability in molecular typing of endometrial carcinoma.Discover oncology · 2026Article
- Lynch Syndrome as a Spectrum of Four Distinct Genetic Disorders: Toward Genotype-Guided Precision Management in the NGS Era.Cancers · 2026Review
- TMB-related immune gene PAEP influences clear cell renal cell carcinoma progression and prognosis.European journal of medical research · 2026Article
- The evolution of vaccine strategies for colorectal cancer: from conventional approaches to the mRNA era.Frontiers in immunology · 2026Review
- Recurrent Pituitary Adenoma Causing Cushing's Disease in a Patient With Lynch Syndrome.Cureus · 2026Article
- KDM3B Predicts Expression Signature, Prognosis Value, and Immune Characteristics of Cancers: A Pan-Cancer Analysis.BioMed research international · 2026Article
- Durable response to dual immune checkpoint blockade in Lynch syndrome-associated serous ovarian carcinoma: a case report.Frontiers in medicine · 2026Article
- Article
- Biomarkers in metastatic castration-resistant prostate cancer for efficiency of immune checkpoint inhibitors.Annals of medicine · 2025Review
- Mismatch Repair as a Dynamic and Clinically Actionable Vulnerability in Cancer.Cancer research · 2025Review
- Biology and evolving management of resectable dMMR/MSI-H cancers: current status and future perspectives.Cancer immunology, immunotherapy : CII · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study.Journal of personalized medicine · 2025Article
- MLH1 and MSH2 expression in endometrial cancer - microscopic and computer assessment of immunohistochemical method.Histology and histopathology · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 9 institutions in 2 countries.
Funding
Abstract
Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.
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