Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.

TitleMethylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.
Publication TypeJournal Article
Year of Publication1997
AuthorsKane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R
JournalCancer Res
Volume57
Issue5
Pagination808-11
Date Published1997 Mar 01
ISSN0008-5472
KeywordsAdaptor Proteins, Signal Transducing, Adenocarcinoma, Base Sequence, Colonic Neoplasms, DNA Methylation, DNA Repair, DNA, Neoplasm, Fungal Proteins, Gene Expression Regulation, Neoplastic, Humans, Molecular Sequence Data, MutL Protein Homolog 1, Promoter Regions, Genetic, Saccharomyces cerevisiae Proteins, Tumor Cells, Cultured
Abstract

Somatic mutations in DNA mismatch repair genes have been observed in sporadic tumors as well as cell lines and xenografts derived from such tumors implicating genetic defects of mismatch repair genes in the development of such tumors. However, the proportion of sporadic tumors in which mismatch repair genes have been inactivated has not been determined accurately. We have analyzed 66 sporadic colorectal tumors for the expression of hMLH1 by immunohistochemistry and identified 4 tumors that do not express hMLH1. These four colorectal tumors, a colon tumor cell line (SW48) and an endometrial tumor cell line (AN3CA), did not express hMLH1, despite the absence of mutations in its coding sequence. Cytosine methylation of the hMLH1 promoter region was found in these four colorectal tumors, whereas cytosine methylation of the hMLH1 promoter region was absent in adjacent normal tissue or in nine tumors that expressed hMLH1. In addition, cytosine methylation of the hMLH1 promoter region was observed in the SW48 and AN3CA cell lines that do not express hMLH1 but not in four tumor cell lines known to express hMLH1 mRNA. Our data indicate that DNA methylation is likely to be a common mode of mismatch repair gene inactivation in sporadic tumors.

Alternate JournalCancer Res
PubMed ID9041175
Grant ListCA06516 / CA / NCI NIH HHS / United States
CA44704 / CA / NCI NIH HHS / United States
CA67151 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700