Complete BRCA mutation screening in breast and ovarian cancer predisposition families from a North-Eastern Romanian population

Breast cancer is the most common cancer in women worldwide, including Romania, where its incidence has increased significantly during the last decade. Ovarian cancer is the fourth leading cause of mortality by cancer in women. BRCA1 and BRCA2 are major cancer predisposition genes, responsible for a large percentage of hereditary breast and ovarian cancer (HBOC) families. We investigated 17 patients from unrelated HBOC families in north-eastern Romania, screening for mutations in BRCA1 and BRCA2 by mutation-specific PCR and by dideoxy sequencing. We identified four BRCA1 and two BRCA2 mutations in the 17 families. The overall mutation frequency was 41% (7/17; 5 BRCA1 and 2 BRCA2). Two mutations (BRCA1 c.2241dupC and BRCA2 c.8680C>T) were novel and not listed in the BIC database. Two recurrent BRCA1 mutations (c.5266dupC and c.181T>G), previously described among Ashkenazi Jewish and Eastern European populations, were also found. Two unclassified variants (UV) were found, one of which was novel (BRCA2 c.4589A>G). Medical follow-up for mutation carriers was implemented. Our study is the first molecular investigation of the role of the BRCA genes in breast and ovarian cancer in Romania.