Ask about this productRelated genes to: MLH1 antibody
- Gene:
- MLH1 NIH gene
- Name:
- mutL homolog 1
- Previous symbol:
- COCA2
- Synonyms:
- HNPCC, FCC2, HNPCC2
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-11-24
- Date modifiied:
- 2019-04-23
Related products to: MLH1 antibody
Related articles to: MLH1 antibody
- Gallbladder adenocarcinoma has limited global prevalence but occurs more frequently in certain regions. The disease is often diagnosed at advanced stages, restricting therapeutic options and contributing to poor outcomes. The molecular mechanisms underlying its development remain largely undefined, complicating the discovery of targeted therapies. Microsatellite instability (MSI), resulting from defective DNA mismatch repair, plays a well-established role in several malignancies; however, its significance in gallbladder adenocarcinoma remains unclear. Characterizing MSI status may help identify patients eligible for novel therapeutic approaches. This study investigates the loss of DNA mismatch repair protein expression in gallbladder adenocarcinoma. - Source: PubMed
Publication date: 2026/03/09
Ghosh RanajoyMondal AninditaHalder AniketRay SukantaChatterjee Uttara - MutS and MutL proteins and their eukaryotic homologs have important functions in DNA metabolism. MutLβ (MLH1-PMS1 heterodimer) is a poorly understood eukaryotic MutL complex. Recent genetic studies have implicated MutLβ in the process of expansion of the short, tandem DNA repeat tracts that is responsible for the repeat expansion diseases. The function of MutLβ and the mechanism of MutLβ-dependent DNA expansions have not been established. We show here that MutLβ promotes MutSβ- and MutLγ-dependent DNA expansions in human cell extracts and defined systems. Importantly, DNA expansions that occur in human cell extracts in the presence of MutSβ and a low concentration of MutLγ require MutLβ. A MutSβ variant lacking the PCNA-binding motif is proficient in supporting MutLβ-promoted and MutLγ-dependent DNA expansions. We also show that MutLβ enhances the MutSβ-dependent endonuclease activity of MutLγ that incises the loop-lacking strand of loop-containing DNAs. MutLβ also increases the endonuclease activity of MutLγ in the presence of ATP-Mn and physically interacts with MutLγ, MutSβ, and PCNA. In addition, MutLβ suppresses inhibition of DNA expansion by MutSα. An MLH1-F80V substitution in MutLβ causes a defect in the ability of the protein to promote MutSβ- and MutLγ-dependent DNA expansions. Taken together, our findings support a model in which MutLβ is involved in DNA expansions by acting in a MutSβ- and MutLγ-dependent mechanism that includes incision of loop-containing DNAs in the loop-lacking strand. - Source: PubMed
Publication date: 2026/04/22
Kadyrova Lyudmila YKadyrov Farid FHayward BruceUsdin KarenKadyrov Farid A - Microsatellite instability (MSI) is a clinically actionable molecular phenotype in cancer, but MSI-associated findings remain fragmented across tumor types, study designs, and biomarker categories, limiting systematic cross-cancer comparison and evidence-guided biomarker prioritization. To address this problem, we developed the Microsatellite Instability Cancer Knowledgebase (MSICKB), a manually curated and literature-traceable resource for MSI-associated molecular and clinical features. We collected and curated 1,382 MSI-related features from 492 publications covering 31 cancer types and organized the evidence into 4 major dimensions: genetic and molecular alterations, clinicopathological features, prognostic factors, and therapeutic response. Based on curated gene-cancer associations, we constructed a simple bipartite network to examine the cross-cancer organization of MSI-associated genes. In the primary network, 99 genes were linked to 13 cancer types through 147 unique gene-cancer edges. Gene degree was strongly right-skewed, with most genes linked to a single cancer type and a small subset showing broader cross-cancer connectivity. Using an operational cutoff of degree ≥ 3, we identified 9 hub genes: BRAF, CD274, KRAS, MLH1, MSH2, PTEN, RNF43, TGFBR2, and TP53. These hubs were enriched in canonical MSI-related pathways, including mismatch repair, cancer signaling, and immune regulation. To provide external molecular support, we further evaluated the hub genes in 3 The Cancer Genome Atlas cohorts with established MSI relevance. In pooled analyses of 336 MSI-high and 1,214 non-MSI-high tumors, all 9 hub genes showed significant differences in mutation prevalence and expression. Overall, MSICKB provides a structured framework for MSI-related evidence synthesis, cross-cancer comparison, and biomarker prioritization and is freely available at http://www.sysbio.org.cn/MSICKB/. - Source: PubMed
Publication date: 2026/04/20
Zhang YuxinLi XiaoyuZheng XinBi ChengSong JieXu ZhichuanCao DanPose Marcos GestalShen Bairong - Multilocus inherited neoplasia alleles syndrome (MINAS) is a rare but increasingly recognized entity characterized by germline pathogenic variants in multiple cancer susceptibility genes, leading to overlapping hereditary cancer syndromes. The growing use of next-generation sequencing (NGS) and comprehensive genetic testing has increased MINAS detection, with an estimated 1.37% prevalence among hereditary cancer patients. Genes commonly implicated include BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, APC, TP53, PTEN, and STK11, conferring a higher risk of multiple primary malignancies. We describe a case of a postmenopausal woman initially diagnosed with Stage IIIB luminal A breast carcinoma, who developed contralateral breast recurrence with supraclavicular and pulmonary metastases, responding completely to ribociclib and letrozole. Given her early-onset breast cancer, genetic testing of her hereditary cancer risk revealed BRCA2 and MLH1 germline variants, confirming MINAS syndrome. Subsequent evaluation identified colonic adenocarcinoma (Stage IIIB, MLH1/PMS2 deficiency), leading to total colectomy, hysterectomy, and bilateral salpingo-oophorectomy. Surveillance was proposed for colon cancer, while ribociclib and letrozole were continued for breast cancer. This case highlights the clinical complexity of MINAS syndrome. The comprehensive genomic profiling is critical for guiding targeted therapy, immunotherapy, and surgical decision-making, optimizing outcomes in this high-risk population. - Source: PubMed
Publication date: 2026/04/19
Avila-Rodriguez VanezaRuiz-Patiño AlejandroBonilla-Gonzalez CarlosAcevedo María Eugenia ManriqueLopez PatriciaDiaz Magda Jimena VargasRubio DiegoGarzon María Alejandra BravoFranco SandraMantilla William - Lynch syndrome (LS) is one of the most widely recognized cancer susceptibility syndromes and is caused by germline mutations of the mismatch repair (MMR) genes , , , and . One of the less commonly known mechanisms is the deletion of the 3' end of the Epithelial Cell Adhesion Molecule () gene, which is closely situated to the gene promoter. Such deletion causes hypermethylation of the gene promoter and leads to its inactivation. This case reports a young adult diagnosed with two metachronous primary tumors due to a germline exon 9 deletion and subsequent gene inactivation, shedding light on one of the most underrecognised pathways of microsatellite instability. - Source: PubMed
Publication date: 2026/03/19
Kalfoutzou AretiRapti CleopatraAlmpanis ZannisBagiokou EleftheriaKalakos NikolaosLagopoulou VasilikiKolintzikis VasileiosOikonomakis AristeidisChaleplidis NikolaosRamfidis Vasileios