BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families.

20118 Background: Germline alterations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancer. In families with BRCA1/2 mutations, identification of mutation carriers is clinically rilevant in view of the options for surveillance and prevention. The general aim of the present research is to contribute to the molecular epidemiology of BRCA1/2 genes in the italian region of Sardinia as a prerequisite for a prevention program based on DNA analysis.,Fifty-two of 172 patients diagnosed with primary invasive breast carcinomas (n = 150) or ovarian cancer (n = 18) and 4 male with breast cancer referring to our departments between 2003 and 2005, had a positive family history for breast and/or ovarian cancer and were selected for BRCA1/2 mutation screening by denaturing high-performance liquid chromatography and DNA sequencing. Onehundred DNAs from healthy women originating from the same geographical area were used as population controls.,We identified 7 BRCA sequence alterations: 3 were already described polymorphisms while 4 novel BRCA variants were found in 11 out of 52 (21%) probands. The BRCA23951del3insAT is a novel deleterious mutation which leads to protein truncation at codon 1258 and co-occurred with the missense BRCA2S2546P in 6 probands originating from the same village and in none of the controls. Segregation analysis suggested the cis-position of the two mutations. All mutation carriers shared a common disease-associated BRCA2 haplotype indicating the presence of a founder effect. The BRCA2N272I was first observed in our population and was found in 3 unrelated probands and in none of 200 control chromosomes. The missense BRCA1E1352K mutation was present in 3 patients from two unrelated families with breast and ovarian cancer cases in three generations.,In the present study, BRCA2 are more recurrent than BRCA1 mutations as reported for the northern part of the island. Our findings provide new epidemiological data that may be useful in defining the prevalence, mutational spectrum and penetrance of BRCA1/2 in the genetically homogeneous population of Sardinia. A comprehensive map of the BRCA mutations may facilitate screening/testing for inherited risk of breast cancer. No significant financial relationships to disclose.