METHYLATION OF THE HMLH1 PROMOTER CORRELATES WITH LACK OF EXPRESSION OF HMLH1 IN SPORADIC COLON TUMORS AND MISMATCH REPAIR-DEFECTIVE HUMAN TUMOR-CELL LINES

Citation
Mf. Kane et al., METHYLATION OF THE HMLH1 PROMOTER CORRELATES WITH LACK OF EXPRESSION OF HMLH1 IN SPORADIC COLON TUMORS AND MISMATCH REPAIR-DEFECTIVE HUMAN TUMOR-CELL LINES, Cancer research, 57(5), 1997, pp. 808-811
Citations number
20
Categorie Soggetti
Oncology
Journal title
ISSN journal
00085472
Volume
57
Issue
5
Year of publication
1997
Pages
808 - 811
Database
ISI
SICI code
0008-5472(1997)57:5<808:MOTHPC>2.0.ZU;2-X
Abstract
Somatic mutations in DNA mismatch repair genes have been observed in s poradic tumors as well as cell lines and xenografts derived from such tumors implicating genetic defects of mismatch repair genes in the dev elopment of such tumors. However, the proportion of sporadic tumors in which mismatch repair genes have been inactivated has not been determ ined accurately. We have analyzed 66 sporadic colorectal tumors for th e expression of hMLH1 by immunohistochemistry and identified 4 tumors that do not express hMLH1. These four colorectal tumors, a colon tumor cell line (SW4S) 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 pro moter region was absent in adjacent normal tissue or in nine tumors th at expressed hMLH1. In addition, cytosine methylation of the hMLH1 pro moter region was observed in tile SW48 and AN3CA cell lines that do no t express hMLH1 but not in four tumor cell lines known to express hMLH 1 mRNA. Our data indicate that DNA methylation is likely to be a commo n mode of mismatch repair gene inactivation in sporadic tumors.