PMID: 16531764Mar 15, 2006Paper

Hypermethylation of the MLH1 promoter with concomitant absence of transcript and protein occurs in small patches of crypt cells in unaffected mucosa from sporadic colorectal carcinoma

Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B
Gerard J NuovoAlbert de la Chapelle

Abstract

Hypermethylation of the MLH1 promoter is present in most sporadic colorectal cancers and leads to the abrogation of MLH1 transcription. The significance of the hypermethylation of the promoter that can be detected in rare foci of cells in the normal colonic epithelium adjacent to the carcinoma is unclear. The purpose of this study was to determine the distribution of hypermethylation of the MLH1 promoter DNA with MLH1 RNA expression by RT in situ PCR and MLH1 protein expression by immunohistochemistry in normal colonic tissues. Hypermethylation of the MLH1 promoter DNA was not evident in sections of normal colon from 10 people with no history of colon cancer. MLH1 RNA and protein were detected diffusely throughout the colonic epithelium in these 10 controls. In comparison, hypermethylation of either of 2 regions of the promoter was evident in the normal mucosa from cases adjacent to adenocarcinoma of the colon. In situ analysis of the DNA methylation showed that there were rare foci that involved small groups of cells, typically toward the middle and surface area of a given crypt. In these areas, small foci of colonic epithelial cells, typically in groups of 5 to 10, were found to lack MLH1 RNA and protein in adjacent serial se...Continue Reading

References

Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
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Aug 31, 2002·Genes, Chromosomes & Cancer·Taiji FurukawaToshihiko Tsukamoto

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Citations

Jul 15, 2006·Gut·J J L WongR L Ward
Jun 27, 2008·Virchows Archiv : an International Journal of Pathology·Annegret MüllerUNKNOWN German HNPCC Consortium, German Cancer Aid Deutsche Krebshilfe
Aug 23, 2012·Molecular Carcinogenesis·Manish Mani SubramaniamManuel Salto-Tellez
Nov 12, 2010·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Remco M van den BergRenske D M Steenbergen
Nov 19, 2013·Seminars in Immunology·Mark S Sundrud, Catherine Trivigno
Feb 16, 2005·La Revue de médecine interne·S OlschwangF Eisinger
Jul 23, 2013·International Immunopharmacology·Hiroki KorenagaTomoya Kono
May 29, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Dong-Sun KimJae Yong Park
Apr 17, 2012·Current Opinion in Immunology·Sharon Veenbergen, Janneke N Samsom
Jun 15, 2007·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Farid E Ahmed
Sep 24, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heather HampelAlbert de la Chapelle

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