LOH AND MUTATION ANALYSIS OF CDKN2 IN PRIMARY HUMAN OVARIAN CANCERS

The CDKN2 gene encodes a cell cycle regulatory protein and is located on chromosome 9p21, a region deleted in a wide variety of primary tumo urs. While mutations in the CDKN2 gene itself are frequently observed in tumour cell lines, they are less common in primary tumours. We have investigated the role of the CDKN2 gene in ovarian cancer by analysis for allelic loss of 9p21 and single-strand conformational polymorphis m analysis of exons I and 2 of CDKN2 in 67 primary ovarian tumours. Lo ss of heterozygosity on 9p21 was frequently observed (24/50 informativ e tumours) and was common in early-stage tumours, suggesting that it i s an early event in ovarian tumorigenesis. Homozygous deletion of the CDKN2 gene was detected in only I tumour. No somatic or germline mutat ions were observed in CDKN2, though a codon 140 polymorphism was detec ted in 2 cases. This suggests that CDKN2 is not involved in ovarian tu morigenesis and that another gene(s) may be the target of the frequent 9p allelic losses observed. (C) 1995 Wiley-Liss, Inc.