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
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.