Distinct promoter hypermethylation of p16INK4a, CDH1, and RAR-beta in intestinal, diffuse–adherent, and diffuse–scattered type gastric carcinomas
Article first published online: 10 JUN 2002
Copyright © 2002 John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 198, Issue 1, pages 55–59, September 2002
How to Cite
Oue, N., Motoshita, J., Yokozaki, H., Hayashi, K., Tahara, E., Taniyama, K., Matsusaki, K. and Yasui, W. (2002), Distinct promoter hypermethylation of p16INK4a, CDH1, and RAR-beta in intestinal, diffuse–adherent, and diffuse–scattered type gastric carcinomas. J. Pathol., 198: 55–59. doi: 10.1002/path.1170
- Issue published online: 7 AUG 2002
- Article first published online: 10 JUN 2002
- Manuscript Accepted: 15 APR 2002
- Manuscript Revised: 19 DEC 2001
- Manuscript Received: 20 SEP 2001
- DNA methylation;
- gastric carcinoma
Hypermethylation of CpG islands in gene promoters is associated with silencing of various tumour suppressor genes. Recent studies of colorectal and gastric carcinomas have defined a CpG island methylator phenotype (CIMP), which involves the targeting of multiple genes by promoter hypermethylation. In this study, methylation-specific polymerase chain reaction (PCR) was performed to study methylation of CpG islands in the promoters of the p16INK4a, cadherin 1 (CDH1), and retinoic acid receptor-beta (RAR-beta) genes in 45 gastric carcinomas and to investigate whether CDH1 and RAR-beta promoter hypermethylation is associated with CIMP-positive gastric carcinoma. CpG island hypermethylation of the p16INK4a, CDH1, and RAR-beta promoters was detected in 12 (27%), 26 (58%), and 24 (53%) of the 45 gastric carcinomas, respectively. Hypermethylation of the p16INK4a promoter was more common in intestinal type than in diffuse type gastric carcinomas (p = 0.0023; Fisher's exact test) and was inversely associated with p53 mutations (p = 0.0225; Fisher's exact test). However, CDH1 and RAR-beta promoter hypermethylation was observed more frequently in diffuse–scattered type gastric carcinoma than in other types (intestinal and diffuse–adherent types) (p = 0.0175 and p = 0.0335, respectively; Fisher's exact test) and was not associated with p53 mutation status. Moreover, hypermethylation of the CDH1 and RAR-beta promoters occurred concordantly (p < 0.0001; Fisher's exact test). These results suggest that at least two types of promoter methylation status are involved in the development of the intestinal (p16INK4a promoter hypermethylation) and diffuse–scattered types (CDH1 and RAR-beta promoter hypermethylation) of gastric carcinoma. Copyright © 2002 John Wiley & Sons, Ltd.