Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer
2006
Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the hypermethylation of the promoter regions of five genes: hMLHI, APC, E-cadherin, RAR-fi and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLHI, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-fi in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLHI and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLHI, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.
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