Alteration of p16 and p15 genes in common epithelial ovarian tumors

✍ Scribed by Masami Fujita; Takayuki Enomoto; Tomoko Haba; Ryuichi Nakashima; Makoto Sasaki; Kiyoshi Yoshino; Hiroko Wada; Gregory S. Buzard; Noboru Matsuzaki; Kenichi Wakasa; Yuji Murata

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 244 KB
• Volume: 74
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970422)74:2<148::aid-ijc2>3.0.co;2-z

✦ Synopsis

We have examined the roles of 2 putative tumor-suppressor genes, the p16 and p15 inhibitor-of-cyclin-dependentkinase genes, in the most commonly occurring epithelial tumors of the human ovary. Expression of p16 mRNA, examined by RT-PCR, was significantly reduced in 15 of the 48 tumors. Aberrant expression of p16 protein, detected by immunohistochemistry, occurred in 22 of 60 tumors, more frequently in low-grade tumors, and had significant correlation with low p16 mRNA expression. Hypermethylation of a site within the 58-CpG island of the p16 gene was significantly associated with loss of p16 mRNA and protein expression. Homozygous gene deletion, evaluated by differential PCR analysis, was found in 2 tumors for the p16 gene and in 1 tumor for the p15 gene among 70 ovarian tumors examined. PCR-SSCP analysis detected point mutations in p16 in 4 tumors and in p15 in 1 tumor. One was a 38-bp deletion, from codons 48 to 60, in a mucinous tumor of low malignant potential; another was a non-sense mutation in codon 60 in a mucinous adenocarcinoma. The remaining 2 mutations were mis-sense mutations, one in codon 58 and the other in codon 60, in 2 endometrioid adenocarcinomas. We conclude that inactivation of p16, by loss of p16 mRNA and protein expression as a consequence of hypermethylation of the 58-CpG island, rather than by gene deletion or point mutation, may play an important role in the genesis of human ovarian epithelial tumors.