Characteristics of BRCA1 / 2 mutations carriers including large genomic rearrangements in high risk breast cancer patients

Purpose We investigated the prevalence of BRCA1/2 small mutations and large genomic rearrangements in high risk breast cancer patients who attended a genetic counseling clinic. Methods In total 478 patients were assessed for BRCA1/2 mutations by direct sequencing, of whom, 306 were identified as non-carriers of BRCA1/2 mutation and assessed for large rearrangement mutations by multiplex ligation-dependent probe amplification. Family history and clinicopathological characteristics of patients were evaluated. Results Sixty-three mutation carriers (13.2%) were identified with BRCA1 mutations (6.3%) and BRCA2 mutations (6.9%), respectively. Mutation frequency was affected by familial and personal factors. Breast cancer patients with family history of breast and ovarian cancer showed the highest prevalence of BRCA1/2 mutations (67%), and triple-negative breast cancer (TNBC) patients showed high BRCA1 mutation prevalence (25%). The three probands of BRCA1 deletion (1%) represented both familial risk and personal or clinicopathological risk factors as two with TNBC and one with bilateral ovarian cancer. Discussion This is the largest study assessing large genomic rearrangement prevalence in Korea and BRCA1 deletion frequency was low as 1% in patients without BRCA1/2 small mutations. For clinical utility of large genomic rearrangement testing needs further study.