The Molecular Detection of Germline Mutations in the BRCA1 and BRCA2 Genes Associated with Breast and Ovarian Cancer in a Romanian Cohort of 616 Patients

Abstract

The objective of this study was to identify and classify the spectrum of mutations found in the BRCA1 and BRCA2 genes associated with breast and ovarian cancer in female patients in Romania. Germline BRCA1 and BRCA2 mutations were investigated in a cohort of 616 female patients using NGS and/or MLPA methods followed by software-based data analysis and classification according to international guidelines. Out of the 616 female patients included in this study, we found that 482 patients (78.2%) did not have any mutation present in the two genes investigated; 69 patients (11.2%) had a BRCA1 mutation, 34 (5.5%) had a BRCA2 mutation, and 31 (5%) presented different type of mutations with uncertain clinical significance, moderate risk or a large mutation in the BRCA1 gene. Our investigation indicates the most common mutations in the BRCA1 and BRCA2 genes, associated with breast and ovarian cancer in the Romanian population. Our results also bring more data in support of the frequency of the c.5266 mutation in the BRCA1 gene, acknowledged in the literature as a founder mutation in Eastern Europe. We consider that the results of our study will provide necessary data regarding BRCA1 and BRCA2 mutations that would help to create a genetic database for the Romanian population.

Keywords: BRCA1 gene mutation; BRCA2 gene mutation; breast cancer; ovarian cancer.

Figure 1

Distribution of BRCA1 mutations across protein domains (green box—Zinc finger, C3HC4 type (RING finger) domain, red box—Serine-rich domain associated with BRCT, blue box—Ethylene insensitive 3, yellow—BRCA1 C Terminus (BRCT) domain).

Figure 2

Distribution of BRCA2 mutations across protein domains (green boxex—BRCA2 repeat, red box—BRCA2_helical, blue box—BRCA2, oligonucleotide/oligosaccharide-binding, domain 1, yellow box—Tower, purple box—BRCA2, oligonucleotide/oligosaccharide-binding, domain 3).