ArticleJournal of medical genetics2000
The role of hypermethylation of the hMLH1 promoter region in HNPCC versus MSI+ sporadic colorectal cancers.
Article in Journal of medical genetics, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 116 citations in OpenAlex.
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- Human mutL homolog 1 expression characteristic and prognostic effect on patients with sporadic colorectal cancer.International journal of clinical and experimental medicine · 2015Article
- Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer: a descriptive and prognostic cancer marker study.Cellular oncology (Dordrecht, Netherlands) · 2013Article
- Clinico-pathologic Parameters for Prediction of Microsatellite Instability in Colorectal Cancer.Cancer research and treatment · 2012Article
- The Correlation between Microsatellite Instability and the Features of Sporadic Colorectal Cancer in the North Part of Iran.Gastroenterology research and practice · 2012Article
- Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects.American journal of physiology. Gastrointestinal and liver physiology · 2011Article
- Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2011Article
- Lynch syndrome in Tunisia: first description of clinical features and germline mutations.International journal of colorectal disease · 2011Article
- Selection of patients with germline MLH1 mutated Lynch syndrome by determination of MLH1 methylation and BRAF mutation.Familial cancer · 2010Article
- Frequent alterations of the candidate genes hMLH1, ITGA9 and RBSP3 in early dysplastic lesions of head and neck: clinical and prognostic significance.Cancer science · 2010Article
- A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory.Journal of cellular and molecular medicine · 2010Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHypermethylation of the promoter region of the hMLH1 gene is associated with absent expression of MLH1 protein in sporadic colorectal cancers with microsatellite instability (MSI+), and it has been proposed that methylation may be a mechanism of inactivation in Knudson's hypothesis. The incidence of hypermethylation of the hMLH1 promoter in hereditary non-polyposis colorectal cancer (HNPCC) versus MSI+ sporadic colorectal cancer was investigated and compared.
methodsDNA was available from 10 HNPCC colorectal cancers (median age 58 years, range 39-67) with germline mutations in hMLH1 and 10 MSI+ sporadic colorectal cancers (mean age 79 years, range 41-85). MSI was determined by amplification of BAT26 and TGF-beta RII. The methylation status of the hMLH1 promoter was studied by the polymerase chain reaction (PCR) based HpaII restriction enzyme assay technique. Evidence of allelic loss at hMLH1 was searched for in the HNPCC colorectal cancers.
resultsAll cases were confirmed to be MSI+. The promoter region of hMLH1 was hypermethylated in seven of 10 MSI+ sporadic cancers versus 0 of 10 HNPCC cancers (p<0.002). Evidence of loss of heterozygosity at hMLH1 was observed in eight of the 10 HNPCC colorectal cancers.
conclusionWhile mutations and allelic loss are responsible for the MSI+ phenotype in HNPCC cancers, the majority of MSI+ sporadic cancers are hypermethylated in the promoter region of hMLH1. These data further support our argument that tumours from HNPCC patients, which almost always acquire a raised mutation rate, mostly follow a different pathway from MSI+ sporadic tumours.
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