Abstract
BackgroundThe incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region.MethodsWe sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC.ResultsAmong the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41–50 years, BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively).ConclusionsThe overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.
Highlights
The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history
Screening of BReast CAncer susceptibility gene 1 (BRCA1)/BReast CAncer susceptibil‐ ity gene 2 (BRCA2) genes for the identification of pathogenic mutations is essential to provide genetic counseling to the members of affected families, for medical follow-up, and for the targeted therapy selection which is based on the inhibitor of poly-ADP-ribose polymerase inhibitor namely the Olaparib [14]
Patients characteristics A total of 134 breast and/or ovarian cancer subjects were included in this study
Summary
The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. Women carrying pathogenic germline mutations in BRCA1/BRCA2 genes have an increased risk of BOC compared to those with wild type BRCAgenes [11,12,13]. Screening of BRCA1/BRCA2 genes for the identification of pathogenic mutations is essential to provide genetic counseling to the members of affected families, for medical follow-up, and for the targeted therapy selection which is based on the inhibitor of poly-ADP-ribose polymerase inhibitor namely the Olaparib [14]. Despite the importance of the mutational spectrum of BRCA1/ BRCA2 genes, only few studies using Sanger DNA sequencing, investigated Tunisian patients with HBOC. The authors identified 232 and 239 pathogenic sequence variants in BRCA1 and BRCA2, respectively that include only few variants that were found in Tunisian patients [15]
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