LOSS OF HETEROZYGOSITY ON CHROMOSOME-5 IN SPORADIC OVARIAN-CARCINOMA IS A LATE EVENT AND IS NOT ASSOCIATED WITH MUTATIONS IN APC AT 5Q21-22

Frequent loss of heterozygosity in ovarian carcinoma (OC) has been reported on several different chromosomes. We have studied 27 OCs and corresponding normal tissue for loss of heterozygosity (LOH) using 10 markers detecting polymorphisms on chromosome 5 (two on 5p and eight on 5q), Three tumours showed extra copies, rather than loss, of one homologue. Twelve of 24 remaining tumours showed LOH on 5q (50%), and 8 of 21 on 5p (38%). Of the 12 showing LOH on Sq, 7 showed reduction to homozygosity at all informative markers over the chromosome, The remaining 5 showed LOH over all of 5q. These data are consistent with the localisation of a tumour suppressor gene on 5q involved in OC. A good candidate is the APC gene, which is mutated in a number of adeno carcinomas derived from several tissues and is located at 5q21-22. The APC gene was studied in 40 ovarian tumours, including all the OCs showing LOH, by single strand conformation polymorphism (SSCP). Analysis of all the exons containing published mutations (similar to 4.7 kb of the cDNA) did not reveal any band shifts that could be attributed to mutations. However, a new polymorphism was detected, as well as 7 known polymorphisms. Together, these data indicate that (1) LOH is common on chromosome 5 in OC, (2) APC is not mutated in OC, and (3) another gene (or genes) on chromosome 5q is responsible for the LOH seen. (C) 1994 Wiley-Liss, Inc.