MOLECULAR-GENETIC CHANGES ASSOCIATED WITH OVARIAN-CANCER

Multiple specific chromosomal deletions can be found in human epitheli al ovarian cancer by cytogenetic analysis or molecular techniques, Som atic allelic deletion or loss of heterozygosity (LOH) in a tumor is co nsidered circumstantial evidence for the location of tumor suppressor genes. We have examined 27 primary epithelial ovarian tumors for the p resence of LOH at 19 polymorphic markers on chromosomes 1, 5, 6, 9, 11 , 13, and 17. Markers near the adenomatous polyposis coli (APC) gene a t 5q21 showed LOH in 50% (10/20) of informative cases. LOH was seen in 53% (8/15) at the IFNA locus on 9p, another region implicated in othe r tumors, but not previously associated with ovarian cancer. We observ ed LOH for markers on 11p15 in 50% (12/24) of ovarian cancer DNAs from informative cases, while only 25% (4/16) at 11q13 and 29% (5/17) at 1 1q24 showed LOH. Only a portion of distal 11p was deleted in six cases . The incidence of LOH (50%) at HGH (17q22-q24) was greater than that at D17S579 (39%; 17q21), a locus tightly linked to BRCA1. Sixty-four p ercent (7/11) showed allelic loss at 17p11, LOH was infrequently obser ved at markers on chromosomes 1, 6, and 13q. Most cases showing LOH we re stage III or IV, and most showed LOH at more than one locus. These studies support the concept that multiple genetic loci are involved in ovarian tumorigenesis. Two additional regions thought to harbor genes important in other cancers, 5q21 and 9p21, can now be added to the gr owing spectrum of molecular alterations seen in ovarian cancer. (C) 19 94 Academic Press, Inc.