Hereditary copy number variations of BRCA1/2 in breast and ovarian cancers

Abstract

   Testing of hereditary pathogenic variants in the BRCA1/2 genes is standard component of the evaluation of patients with breast cancer and ovarian cancer. Routine DNA testing is limited to the identification of point mutations and microdeletions/insertions, and practically does not take into account other types of aberrations. CNV analysis based on data from a targeted NGS study of DNA samples from patients with breast cancer (n = 3925) and breast cancer (n = 1175) was performed with the gCNV GATK tool. The subsequent verification of bioinformatically predicted CNV of BRCA1/2 exons was carried out by digital droplet PCR. We detected 35/5149 (0.7%) cases with hereditary large rearrangements in the BRCA1 (n = 31) and BRCA2 (n = 4). The most frequent CNV was BRCA1 exon 1-2 del (n = 11). The young age of diagnosis significantly increases the probability of detecting CNV mutations (breast cancer: 21/2294 (0.9 %) vs 6/1631 (0.4 %) p = 0.0247; ovarian cancer: 6/328 (1.8 %) vs 2/847 (0.2 %) p = 0.0062), similarly micromutations in these genes. CNVs account for approximately 5.6 % of all pathogenic variants in the BRCA1 and BRCA2 genes. This indicates the need for integrating CNV analysis into routine diagnosis of hereditary cancer syndromes.