ArticleBMC cancer2018
MLH1-93 G/a polymorphism is associated with MLH1 promoter methylation and protein loss in dysplastic sessile serrated adenomas with BRAF
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.BMC cancer · 2019Pooled it
- The polymorphic variant rs1800734 influences methylation acquisition and allele-specific TFAP4 binding in the MLH1 promoter leading to differential mRNA expression.Scientific reports · 2019Pooled it
- Immune microenvironment evolution across the serrated neoplasia pathway and its relevance to immunotherapy.Frontiers in oncology · 2026Review
- Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite.International journal of medical sciences · 2024Review
- Preliminary exploration of the effects of environmental factors on the microsatellite status of BRAF-mutated colorectal cancer.World journal of surgical oncology · 2023Article
- Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy.Cancers · 2023Review
- Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis.International journal of molecular sciences · 2022Review
- Molecular Oncology in Management of Colorectal Cancer.Indian journal of surgical oncology · 2021Article
- Association between SNPs and Loss of Methylation Site on the CpG island of the Promoter Region of the Smoothened Gene, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Review
- Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.Medical sciences (Basel, Switzerland) · 2018Review
- The role of CDX2, MUC5AC, and p53 in the evaluation of the progression of serrated lesions toward colorectal carcinoma.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologieArticle
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSessile serrated adenomas with BRAF mutation progress rapidly to cancer following the development of dysplasia (SSAD). Approximately 75% of SSADs methylate the mismatch repair gene MLH1, develop mismatch repair deficiency and the resultant cancers have a good prognosis. The remaining SSADs and BRAF mutant traditional serrated adenomas (TSA) develop into microsatellite stable cancers with a poor prognosis. The reason for this dichotomy is unknown. In this study, we assessed the genotypic frequency of the MLH1-93 polymorphism rs1800734 in SSADs and TSAs to determine if the uncommon variant A allele predisposes to MLH1 promoter hypermethylation.
methodsWe performed genotyping for the MLH1-93 polymorphism, quantitative methylation specific PCR, and MLH1 immunohistochemistry on 124 SSAD, 128 TSA, 203 BRAF mutant CRCs and 147 control subjects with normal colonoscopy.
resultsThe minor A allele was significantly associated with a dose dependent increase in methylation at the MLH1 promoter in SSADs (p = 0.022). The AA genotype was only observed in SSADs with MLH1 loss. The A allele was also overrepresented in BRAF mutant cancers with MLH1 loss. Only one of the TSAs showed loss of MLH1 and the overall genotype distribution in TSAs did not differ from controls.
conclusionsThe MLH1-93 AA genotype is significantly associated with promoter hypermethylation and MLH1 loss in the context of SSADs. BRAF mutant microsatellite stable colorectal cancers with the AA genotype most likely arise in TSAs since the A allele does not predispose to methylation in this context.
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