Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early‐onset breast/ovarian cancer from Tunisia

Abstract

The contribution of BRCA1/BRCA2 mutations to hereditary breast cancer in the Tunisian population has not been accurately estimated. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in early onset and familial breast/ovarian cancer among Tunisian women. To identify predictive factors for BRCA1/2 mutations, we screened the entire coding sequences and intron/exon boundaries of BRCA1/BRCA2 genes in 48 patients by direct sequencing. Twelve pathogenic mutations were detected (25%); three in BRCA1 (c.211dupA in four families, c.5266dupC in three families and c.1504_1508delTTAAA in one family) and two novel mutations in BRCA2 (c.1313dupT in two families and c.7654dupT in two families). We also identified 23 different polymorphisms and unclassified variants. These results indicate that our population has a spectrum of recurrent BRCA mutations.

Multicenter cross‑sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations

“…This finding is in line with a Korean study conducted across 36-centers (22.3%) (17). The mutation rate appears generally lower compared to Western countries (23~35.3%) (18)(19)(20)(21)(22), but higher compared to Peking or Shanghai regions (10.5~18.2%) (23)(24)(25). Lower prevalence of BRCA mutation is in line with comparisons of BC incidence with the Western countries.…”

Molecular characterization, homology modeling and docking studies of the R2787H missense variation in BRCA2 gene: Association with breast cancer

“…However, data from our previous study reported a higher frequency of UVs, about 37% (Riahi et al 2013). Therefore, in our population, the characterization of the impact of such variants is of great importance.…”

“…In order to provide more accurate assessment of the breast cancer risk, the characterization of the functional impact of UVs is a decisive step especially for populations with high rates of UVs as the Tunisian one where UVs account for 37% of all identified BRCA variations (Riahi et al 2013). In this case, non-informative results can be a source of anxiety.…”

“…To address this matter, we assessed the incidence of LOH at the BRCA loci in familial breast tumors. We performed LOH analysis in 48 high-risk breast and ovarian cancer families who had been previously screened for the BRCA1/2 genes (Riahi et al 2013); 12 patients (25%) harbored deleterious mutations (8 in BRCA1 and 4 in BRCA2), 13 carried an unclassified variant in either of the BRCA1/2 genes and 30 were heterozygous for any common polymorphism in these genes. The same, the rate of spontaneous LOH at the BRCA loci in the familial cases not associated with these genes but heterozygous for a polymorphism in BRCA1 (11 cases) or BRCA2 (7 cases) was determined.…”

Clinical applications of next generation sequencing in cancer: from panels, to exomes, to genomes

“…The findings between differing repeat lengths showed that shorter CAG repeats may play protective roles against breast cancer, as opposed to longer repeat lengths, which may contribute to cancer development (Gottlieb et al, 2013). The study demonstrates that merely identifying genetic variations does not provide sufficient understanding of cancer etiology; rather it is necessary to determine frequency and distribution of mutations between cancerous and normal tissues (Gottlieb et al, 2013; Riahi et al, 2014). …”