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
- To evaluate the prognostic significance of mismatch repair (MMR) markers in head and neck squamous cell carcinoma (HNSCC) patients. We performed a systematic review of prognostic factors following PRISMA 2020 using the PI(E)COS framework. Observational studies evaluating MMR protein expression (MSH2, MLH1, MSH6, PMS2) in HNSCC were identified through searches in five databases and gray literature. Eligible studies were qualitatively synthesized. Risk of bias was assessed using the QUIPS tool. Seven observational studies involving 846 HNSCC patients met the eligibility criteria. Most patients were males (78.3%), the age ranged from 59 to 63.6 years, and the oral cavity was the most common tumor site. MMR protein expression associated with clinicopathological features was heterogeneous, with prognostic effects varying according to tumor subsite, HPV/p16 status, and analytical approach. Across the available studies, low or loss of MSH2 expression was consistently associated with poorer overall survival, with reported hazard ratios ranging from 2.75 to 4.38, all indicating a clinically meaningful increased risk of death. In contrast, the prognostic value of MLH1, MSH6, and PMS2 varied by tumor subsite, HPV/p16 status, and patient age, lacking sufficient consistency for quantitative pooling. Due to the limited number of methodologically comparable studies, a quantitative meta-analysis was not appropriate. In conclusion, the pooled results showed that reduced or absent MSH2 expression is linked to poorer outcomes in HNSCC, suggesting that MSH2 may be the most promising prognostic biomarker, pending further validation. - Source: PubMed
Publication date: 2026/08/11
de Carvalho Gomes José RenatoCosta Raisa Ferreirade Lima-Souza Reydson AlcidesAntolini-Tavares ArthurTincani Alfio JoséChone Carlos TakahiroAltemani AlbinaMariano Fernanda Viviane - CpG dinucleotides are mutational hotspots due to spontaneous deamination of 5-methylcytosine (5mC), resulting in T:G mismatches that can lead to CpG>TpG transitions. These mutations are a hallmark of aging and cancer and play a central role in the evolution of vertebrate genomes. We have previously uncovered MBD4 as the primary base excision repair (BER) glycosylase responsible for 5mC deamination repair. Here, we employ an APOBEC1 deaminase fused to a catalytically dead Cas9 to induce targeted 5mC deamination independently of DNA replication and track its repair in human cells. This approach reveals that MBD4 elicits a coordinated repair response with a non-canonical branch of mismatch repair (MMR) involving complexes MutLβ (MLH1-PMS1) and MutSα (MSH2-MSH6). We uncover the physical interaction between MBD4 and MutLβ and demonstrate that MBD4-mediated repair requires MLH1. We show that PMS1 deficiency phenocopies the CpG>TpG hypermutation signature characteristic of MBD4 loss, establishing 5mC deamination repair as a key function of human PMS1. In alignment with our experimental data, we show that the CpG>TpG mutational burden in MMR-deficient tumors is partly explained by replication-independent processes. Altogether, we uncover a novel function of non-canonical MMR that underscores its interplay with BER in safeguarding genomic integrity against damage to methylated DNA. - Source: PubMed
Le Ven AnaïsVanhuele SandraGanier OlivierHouy AlexandreKahn AmandaRodrigues ManuelStern Marc-HenriGuerois RaphaelSilveira André Bortolini - Colorectal cancer (CRC) is a heterogeneous disease shaped by genetic and epigenetic alterations. Approximately 20% of CRCs exhibit widespread CpG island hypermethylation, termed the CpG Island Methylator Phenotype (CIMP), frequently accompanied by promoter hypermethylation, deficient mismatch repair (dMMR) and microsatellite instability (MSI). However, methylation patterns associated with MSI, independent of CIMP and silencing, and the influence of anatomical location and patient age on the CRC methylome remain incompletely defined. We performed epigenome-wide DNA methylation profiling of 259 sporadic CRCs using the Illumina EPICv2 array. Differential methylation between MSI and microsatellite stable (MSS) CRCs was assessed after adjustment for tumour purity and anatomical location, then promoter methylation and CIMP status, to delineate MSI-associated methylation changes. Additionally, we evaluated the effects of anatomical location and age on methylation patterns. While differential methylation between MSS and MSI CRCs was dominated by promoter hypermethylation, additional adjustment for hypermethylation and CIMP identified 656 CpG sites associated with MSI, beyond the global methylator phenotype. These included hypermethylation at , , and , identifying differential methylation of genes involved in WNT signalling and transcriptional regulation. Within MSI CRCs, we observed the co-occurrence of hypermethylation with promoter hypermethylation at . Anatomical location was strongly associated with methylation, whereas age had more modest effects. These results identify methylation changes associated with sporadic MSI beyond CIMP status and hypermethylation, reveal heterogeneity within MSI CRCs, and indicate that anatomical location is a major determinant of the CRC methylome, advancing molecular stratification of CRC. - Source: PubMed
Publication date: 2026/08/10
Ward RebeccaEndicott MollyMallabar-Rimmer BethanBurrage JoeSherwood KittyHuang QiwenWard Joseph CThorn SteveWoolley ConnorWood Sophie JDempster EmmaGreen Harry DTomlinson IanWebster Amy P - MutL homolog 1 (MLH1) is a key component of the mismatch repair (MMR) pathway, and promoter methylation-mediated silencing is a well-established oncogenic mechanism in several tumor types. However, its prevalence and prognostic relevance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. - Source: PubMed
Publication date: 2026/08/10
Silva Fábio França Vieira EDi Domenico MarinaPrada-Ramallal GuillermoSuárez-Peñaranda José ManuelBallini AndreaPadín-Iruegas María Elena - Colorectal cancer is predominantly an adult malignancy and is extremely rare in children. In pediatric patients, it is often associated with genetic predisposition syndromes such as Lynch syndrome or familial adenomatous polyposis. We report the case of a 15-year-old patient admitted for progressively worsening peri-umbilical abdominal pain. Thoraco-abdomino-pelvic computed tomography (CT) revealed parietal thickening of the right third of the transverse colon associated with deep lymphadenopathy and a focal lesion in segment III of the liver. The patient underwent a colonic biopsy, which revealed intramucosal colorectal adenocarcinoma. The clinical course was complicated by bowel obstruction requiring surgery, during which a diverting ileostomy, liver biopsy, and mesenteric lymph node resection were performed. Histopathological examination confirmed metastatic involvement from the primary colonic tumor. Immunohistochemical analysis demonstrated microsatellite instability (MSI) (loss of MLH1/PMS2). The patient subsequently received treatment with pembrolizumab. - Source: PubMed
Publication date: 2026/07/10
El Maoudda HoudaZouiten OthmaneDaher BilaneAfani LeilaEl Fadli MohamedBelbaraka Rhizlane