Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia
Abstract
Background
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. However, the spectrum of
BRCA
mutations remains little explored in Tunisian patients in particular in the southern region.
Methods
We sequenced the entire coding regions of
BRCA1
and
BRCA2
genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC.
Results
Among 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).
Conclusions
The 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.
