Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia

Abstract

AbstractBackgroundThe 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 ofBRCAmutations remains little explored in Tunisian patients in particular in the southern region.MethodsWe sequenced the entire coding regions ofBRCA1andBRCA2genes 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 areBRCA1mutation carriers and 9 areBRCA2mutation 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 inBRCA2and 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 inBRCA1and 2 inBRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) inBRCA2exon 27.BRCAcarriers 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,BRCA1mutations occurred more frequently in patients with OC than those with BC, and converselyBRCA2carriers 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 inBRCA2gene and the c.5030_5033 delCTAA inBRCA1gene 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.