Methylation of specific CpG sites in the promoter region could significantly down-regulate p16(INK4a) expression in gastric adenocarcinoma

Citation
Sh. Song et al., Methylation of specific CpG sites in the promoter region could significantly down-regulate p16(INK4a) expression in gastric adenocarcinoma, INT J CANC, 87(2), 2000, pp. 236-240
Citations number
19
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
00207136 → ACNP
Volume
87
Issue
2
Year of publication
2000
Pages
236 - 240
Database
ISI
SICI code
0020-7136(20000715)87:2<236:MOSCSI>2.0.ZU;2-U
Abstract
Silencing of p16(INK4a) by methylation of the CpG islands in the promoter r egion has been found to be an alternative mechanism of inactivation in seve ral tumors. However, in gastric carcinoma, the relationship between methyla tion status and the transcriptional silencing of the p16 gene remains to be clarified. In this study, we investigated whether methylation of a few spe cific CpG sites in the promoter region could significantly down-regulate p1 6 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 methyl ated CpG sites at the promoter region of p16, In addition, we analyzed the p16-protein expression of 28 primary gastric carcinomas and their normal co unterparts 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 promote r sites. Taken together, these results suggest a strong correlation between de novo methylation of a few specific CpG sites and transcriptional silenc ing of the p16 gene in gastric carcinoma. Int. J, Cancer 87:236-240, 2000, (C) 2000 Wiley-Liss. Inc.