RATES OF JEWISH ANCESTRAL MUTATIONS IN BRCA1 AND BRCA2 IN BORDERLINE OVARIAN-TUMORS

Background: Germline mutations in the BRCA1 and BRCA2 genes are known to be associated with an increased risk of breast and elpithelial ovar ian cancers. Two specific mutations, 185delAG-BRCA1 and 61.74delTBRCA2 , have been detected in a substantial proportion (20%-60%) of unselect ed Ashkenazi Jewish patients i.e., Jewish patients of Eastern/ Norther n European descent-with invasive ovarian cancer and in a measurable pr oportion (2%) of the general Ashkenazi Jewish population. However, unc ertainty exists concerning the heritable basis of borderline ovarian t umors and whether these tumors represent an early form of ultimately i nvasive disease. To gain insight into these issues, we determined the rates of 185delAG-BRCA1 and 6174delT-BRCA2 mutations in patients with borderline ovarian tumors. Methods: Analysis of 185delAG-BRCA1 and 617 4delT-BRCA2 germline mutations was performed by use of a heteroduplex formation assay in samples from 46 consecutive patients with borderlin e ovarian tumors and 59 consecutive patients with invasive epithelial ovarian cancers. Forty-eight samples were also analyzed by restriction enzyme analysis for the presence of the 5382insC-BRCA1 mutation, a mu tation detected in 2.2% of Ashkenazi Jewish patients with breast, but not ovarian, cancer. Results: One (2.2%) of the 46 patient with border line tumors was identified as a carrier of the 185delAG-BRCA1 mutation , and no patients were found to carry the 6174delT-BRCA2 mutation. Nin eteen (32%) of the 59 patients with invasive ovarian cancer were found to carry one of these two mutations; 17 carried 185delAG-BRCA1 and tw o carried 6174delT-BRCA2 (X-2 test with continuity correction, P =.000 28), None of the patients analyzed for 5382insC-BRCA1 were found to ca rry the mutation. In one high-risk family that included 185delAG-BRCA1 carriers, a single patient with stage IIIc borderline ovarian tumor d id not carry the mutation. Conclusions: Invasive epithelial and border line ovarian tumors appear to differ in their genetic predisposition a nd in the molecular mechanisms underlying their genesis.