RARE MUTATIONS AND NO HYPERMETHYLATION AT THE CDKN2A LOCUS IN EPITHELIAL OVARIAN-TUMORS

The tumour-suppressor gene CDKN2A (p16, MTS1, CDK41) encodes a cell cy cle-regulatory protein and is located on chromosome 9p21, a region del eted in a wide variety of human cancers, To determine the role of the CDKN2A gene in the development of ovarian adenocarcinomas, we examined a large series of benign, low malignant potential (LMP) and invasive ovarian neoplasms for evidence of loss of heterozygosity (LOH), homozy gous deletions, point mutations and hypermethylation of the CDKN2A loc us, We have previously reported LOH on 9p in 45% of malignant ovarian neoplasms and a smaller percentage of benign and LMP tumours, In the c urrent study, 6 malignant tumours were identified with partial deletio ns of 9p21. In 5 of these, the CDKN2A gene lays within the minimal del eted region, Homozygous deletions of CDKN2A were observed in only 2/88 invasive ovarian tumours and in 5/11 ovarian cancer cell lines. Of 15 primary ovarian tumours analyzed, one nonsense mutation was identifie d in a mucinous LMP tumour, No evidence of hypermethylation of the CDK N2A gene was found in 50 primary ovarian adenocarcinomas nor in 3 ovar ian cancer cell lines, In conclusion, homozygous deletions, mutations and the de novo methylation of 5' CpG island are not frequent modes of inactivation of the CDKN2A gene in ovarian cancer, The target of 9p L OH in ovarian adenocarcinomas is therefore unknown. (C) 1997 Wiley-Lis s, Inc.