A COMMON REGION OF DELETION ON CHROMOSOME 17Q IN BOTH SPORADIC AND FAMILIAL EPITHELIAL OVARIAN-TUMORS DISTAL TO BRCAI

Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region o n chromosome 17q containing a candidate tumor-suppressor gene (referre d to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heteroz ygosity (LOH) at 21. loci on chromosome 17 (7 on 17p and 14 on 17q). L OH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian can cer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of mar kers positioned telomeric to BRCA1 resulted in the highest degree of L OH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating a llelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tu mors (unique patient number [UPN] 57 and UPN 79) retained heterozygosi ty for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S 74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that s pans similar to 25 cM. These results suggest that a potential tumor-su ppressor gene involved in both sporadic and familial ovarian cancer ma y reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.