Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer.
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: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta 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 hMLH1 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 hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.
Banno
Kouji
K
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. kbanno@sc.itc.keio.ac.jp
Yanokura
Megumi
M
Susumu
Nobuyuki
N
Kawaguchi
Makiko
M
Hirao
Nobumaru
N
Hirasawa
Akira
A
Tsukazaki
Katsumi
K
Aoki
Daisuke
D
D019175:DNA Methylation; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic