A 400 KB NOVEL DELETION UNIT CENTROMERIC TO THE BRCA1 GENE IN SPORADIC EPITHELIAL OVARIAN-CANCER

Allelic deletions on chromosome 17q21 in sporadic ovarian cancer are c ommon, suggesting that inactivation of a tumor suppressor gene(s) in t hat region may be important for the etiology of these tumors. The rece ntly identified BRCA1 gene on 17q21, involved in the development of fa milial breast/ovarian cancer, could be a candidate. However, inactivat ing mutations on BRCA1 in sporadic ovarian cancer has been rarely desc ribed. Furthermore, the potential relationship of BRCA1 gene to ovaria n tumors of borderline malignancy remains also unclear. We constructed a highly detailed deletion map of chromosome 17q21 based on PCR ampli fication of eight polymorphic tandem repeat markers in a 650 kb area i ncluding three BRCA1 intragenic markers. DNA from 52 sporadic ovarian cancers and 26 borderline tumors, together with their corresponding no rmal control tissues were used. Only one borderline tumor showed loss of heterozygosity at one marker, whereas 65% of invasive ovarian cance rs displayed allelic loss in at least one of the markers studied. A co mmon deletion unit, located approximately 60 kb centromeric to BRCA1, was revealed. These results suggest that inactivation of the BRCA1 gen e may not be responsible for the development of borderline ovarian tum ors and that another tumor suppressor gene, located centromeric to the BRCA1 gene, may play a role in sporadic ovarian cancer development.