Premium
Methylation of the hMLH 1 promoter in familial gastric cancer with microsatellite instability
Author(s) -
Yanagisawa Yuka,
Akiyama Yoshimitsu,
Iida Satoru,
Ito Emi,
Nomizu Tadashi,
Sugihara Kenichi,
Yuasa Yasuhito,
Maruyama Kazuo
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000101)85:1<50::aid-ijc9>3.0.co;2-e
Subject(s) - microsatellite instability , dna mismatch repair , biology , carcinogenesis , methylation , epigenetics , dna methylation , gene , cancer research , microbiology and biotechnology , genetics , cancer , promoter , germline mutation , microsatellite , mutation , gene expression , dna repair , allele
Microsatellite instability (MSI), which is recognized as an important mechanism in tumorigenesis, has been reported in familial gastric cancers (FGC). However, genetic defects responsible for this phenotype, that is, mutations in mismatch‐repair genes such as hMLH1 and hMSH2, have not been detected in most FGC cases. Earlier studies have shown that the promoter region of the hMLH1 gene was methylated in some sporadic colorectal and endometrial cancers. To determine how FGC acquire MSI, we examined the MSI status, hMLH1‐protein expression and methylation status of the hMLH1 ‐promoter region in FGC cases. Out of 9 cancers, 6 from 8 FGC kindreds showed MSI at one or more loci; no germline mutations in the hMLH1 or hMSH2 genes were detected; 4 cancers exhibiting MSI displayed aberrant hMLH1 expression: complete loss in one, decreased level in another, and partially staining pattern in the remaining 2. Methylation in the hMLH1 ‐promoter region was found in these 4 cases. In contrast, the cancers displaying hMLH1‐protein expression were not methylated in the hMLH1 ‐promoter region. Our data show a significant association between the absence of hMLH1 expression and methylation of its promoter in FGC cases with MSI. This suggests that the mechanism of inactivation of hMLH1 is epigenetic and that there are other genes responsible for FGC. Int. J. Cancer 85:50–53, 2000. © 2000 Wiley‐Liss, Inc.