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Methylation of specific CpG sites in the promoter region could significantly down‐regulate p16 INK4a expression in gastric adenocarcinoma
Author(s) -
Song Sang Hyun,
Jong HyunSoon,
Choi Hyun Ho,
Kang Shin Hyeok,
Ryu Min Hee,
Kim Noe Kyeong,
Kim WooHo,
Bang YungJue
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 - 10.1002/1097-0215(20000715)87:2<236::aid-ijc14>3.0.co;2-m
Subject(s) - methylation , cpg site , gene silencing , biology , dna methylation , bisulfite sequencing , carcinogenesis , cancer research , microbiology and biotechnology , promoter , gene expression , gene , genetics
Silencing of p16 INK4a by methylation of the CpG islands in the promoter region has been found to be an alternative mechanism of inactivation in several tumors. However, in gastric carcinoma, the relationship between methylation status and the transcriptional silencing of the p16 gene remains to be clarified. In this study, we investigated whether methylation of a few specific CpG sites in the promoter region could significantly down‐regulate p16 activity in the tumorigenesis of gastric carcinoma. By Southern analysis and bisulfite‐modified genomic sequencing of 9 gastric‐carcinoma cell lines, we found that the 5 cell lines (55.5%) not expressing p16 mRNA had methylated CpG sites at the promoter region of p16. In addition, we analyzed the p16‐protein expression of 28 primary gastric carcinomas and their normal counterparts by immunohistochemical staining (IHC) on paraffin sections. Loss of p16 expression was detected in 6 cases (22%). In 5 out of these 6 (83%), the actual p16 gene was inactivated by de novo methylation of the promoter sites. Taken together, these results suggest a strong correlation between de novo methylation of a few specific CpG sites and transcriptional silencing of the p16 gene in gastric carcinoma. Int. J. Cancer 87:236–240, 2000. © 2000 Wiley‐Liss, Inc.