ArticleCellular oncology (Dordrecht, Netherlands)2013
Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer: a descriptive and prognostic cancer marker study.
Article in Cellular oncology (Dordrecht, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis.EBioMedicine · 2024Pooled it
- Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.Clinical epigenetics · 2018Pooled it
- Null Mismatch Repair Proteins Expression Reveals the Temporal Molecular Events in Lynch Syndrome-Related Cancers.Diagnostics (Basel, Switzerland) · 2024Article
- Review
- Article
- Making Sense of the Epigenome Using Data Integration Approaches.Frontiers in pharmacology · 2019Review
- Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives.Seminars in cancer biology · 2018Review
- Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy.World journal of gastroenterology · 2016Review
- Validation of DNA promoter hypermethylation biomarkers in breast cancer--a short report.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer.World journal of gastroenterology · 2014Review
- Epigenetic alterations in a gastric leiomyoma.Case reports in gastrointestinal medicine · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim of this study was to determine in detail how DNA methylation regulates MLH1 expression and impacts clinical management.
methodsColorectal cancer samples were collected from 210 patients. The laboratory methods used to study these samples included methylation specific multiplex ligation-dependent probe amplification (MS-MLPA), real-time quantitative PCR (qPCR), and immunohistochemistry (IHC).
resultsWe found that the MLH1 mRNA and protein expression levels were highly related. MS-MLPA was successful in tumors from 195 patients. In these tumors, hypermethylation was observed in promoter regions A (n = 57), B (n = 30), C (n = 28), and D (n = 47), and in intron 1 (n = 25). The promoter region C and intron 1 methylation levels were found to be excellently suited for discriminating between low and high gene expression levels, whereas those of promoter regions A, B and D were less specific. Hypermethylation in any region (n = 77) served as an independent prognostic factor (hazard ratio 0.56, 95 % confidence interval 0.36-0.89, p = 0.01).
conclusionsMLH1 inactivation through hypermethylation was found to be related to improved survival. Hypermethylation in promoter region C and intron 1 served as the most specific markers for this inactivation.
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