GERMLINE BRCA1 MUTATIONS IN PATIENTS FROM 36 FAMILIES WITH BREAST ANDOR OVARIAN CANCERS IN NORTHERN FRANCE/

The BRCA1 gene modification is responsible for an autosomal dominant s yndrome of inherited early onset breast and/or ovarian cancer. This ge ne is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about I out of 500 women may carry BRCA1 mutation. The BRCA1 gen e war isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected; individuals. We looked by systematic sequencing at BRCA1 germline mutations in 36 pat ients treated at the Centre Oscar-Lambret for breast and/or ovarian ca ncer and that belonged to high risk families. We have found 24 mutatio ns: 9 true mutations inducing modifications of the BRCA1 protein (BRCA 1(+)), 5 mutations with unknown consequences on the BRCA1 protein and 10 mutations corresponding to polymorphisms that had been previously d escribed. All the BRCA1(+) cases had a HPG3 tumor. The median age of d iscovery and the receptor positivity percentage are lower in hereditar y breast cancer than in the standard population of the breast cancers treated in our center. Consequently, BRCA1 mutations are associated to parameters thought to be of bad prognosis.