{"doi":"10.1093/carcin/bgm228","title":"Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics","abstract":null,"journal":"Carcinogenesis","year":2008,"id":604061,"datarank":0.9092185378392027,"base_score":6.061456918928017,"endowment":6.061456918928017,"self_citation_contribution":0.9092185378392027,"citation_network_contribution":0.0,"self_endowment_contribution":0.9092185378392027,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":428,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":172238,"name":"Hiroyuki Yamamoto","orcid":null,"position":1,"is_corresponding":false},{"id":167366,"name":"Kohzoh Imai","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics","abstract":"DNA mismatch repair (MMR) deficiency results in a strong mutator phenotype and high-frequency microsatellite instability (MSI-H), which are the hallmarks of tumors arising within Lynch syndrome. MSI-H is characterized by length alterations within simple repeated sequences, microsatellites. Lynch syndrome is primarily due to germline mutations in one of the DNA MMR genes; mainly hMLH1 or hMSH2 and less frequently hMSH6 and rarely hPMS2. Germline hemiallelic methylation of MLH1, termed epimutation, has been reported to be a new cause of Lynch syndrome. MSI-H is also observed in approximately 15% of colorectal, gastric and endometrial cancers and in lower frequencies in a minority of other tumors, where it is associated with the hypermethylation of the promoter region of hMLH1. MSI-H underlies a distinctive tumorigenic pathway because cancers with MSI-H exhibit many differences in genotype and phenotype relative to cancers without MSI-H, irrespective of their hereditary or sporadic origins. Genetic, epigenetic and transcriptomic differences exist between cancers with and those without the MSI-H. The BRAF V600E mutation is associated with sporadic MSI-H colorectal cancers (CRCs) harboring hMLH1 methylation but not Lynch syndrome-related CRCs. The differences in genotype and phenotype between cancers with and those without MSI-H are likely to be causally linked to their differences in biological and clinical features. Therefore, the diagnosis of MSI-H in cancers is thus considered to be of increasing relevance, because MSI-H is a useful screening marker for identifying patients with Lynch syndrome, a better prognostic factor and could affect the efficacy of chemotherapy. This review addresses recent advances in the field of microsatellite instability research.","is_dataset_classified":null,"base_score":6.061456918928017,"endowment":6.061456918928017,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17942460","pmcid":null,"openalex_id":"https://openalex.org/W2131348295","authors":[],"funders":[],"total_grants":0,"fwci":11.5256,"citation_percentile":0.99035438,"influential_citations":0,"citation_trend":[{"year":2012,"count":15},{"year":2013,"count":23},{"year":2014,"count":34},{"year":2015,"count":33},{"year":2016,"count":39},{"year":2017,"count":28},{"year":2018,"count":18},{"year":2019,"count":23},{"year":2020,"count":31},{"year":2021,"count":24},{"year":2022,"count":14},{"year":2023,"count":23},{"year":2024,"count":16},{"year":2025,"count":14},{"year":2026,"count":4}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/carcin/article-pdf/29/4/673/19255041/bgm228.pdf","host_type":"journal"},{"url":"https://academic.oup.com/carcin/article-pdf/29/4/673/19255041/bgm228.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/carcin/article-pdf/29/4/673/19255041/bgm228.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/carcin/bgm228","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17942460","host_type":"repository"}],"fields_of_study":["Genetic factors in colorectal cancer","Cancer Genomics and Diagnostics","Colorectal Cancer Screening and Detection","Colorectal Neoplasms","Colorectal Neoplasms, Hereditary Nonpolyposis","DNA Methylation","DNA Mismatch Repair","Epigenesis, Genetic","Gene Frequency","Germ-Line Mutation","Humans","Microsatellite Instability","Models, Genetic","Neoplasms","Prognosis"],"mesh_terms":["Colorectal Neoplasms, Hereditary Nonpolyposis","Gene Frequency","Humans","Models, Genetic","Neoplasms","Prognosis","Colorectal Neoplasms","Germ-Line Mutation","DNA Methylation","Epigenesis, Genetic","Microsatellite Instability","DNA Mismatch Repair"],"keywords":["Microsatellite instability","Lynch syndrome","DNA mismatch repair","MLH1","Epigenetics","DNA methylation","Germline mutation","Biology","Genetics","Cancer research","Carcinogenesis","Cancer","Germline","Colorectal cancer","Microsatellite","Mutation","Allele","Gene","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T23:17:07.917077Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}