Methylation of the hMLH1 Promoter Correlates with Lack of Expression of hMLH1 in Sporadic Colon Tumors and Mismatch Repair-defective Human Tumor Cell Lines
MF Kane, M Loda, GM Gaida, J Lipman, R Mishra… - Cancer research, 1997 - AACR
MF Kane, M Loda, GM Gaida, J Lipman, R Mishra, H Goldman, JM Jessup, R Kolodner
Cancer research, 1997•AACRSomatic 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 …
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 …
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 methlation 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.
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