153P - Discovery of new BRCA1/2 mutations not described in the international breast consortium

Background

Genetic testing of patients with family history for breast/ovarian cancer (BOC) have become standard clinical management in Western countries, however, in Tunisia studies of BRCA-associated breast/ovarian cancer remain less investigated. The aim of our study was to detect BRCA mutation notably those not described in the international breast consortium.

Methods

We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with breast/ovarian cancer.

Results

Pathogenic BRCA1/BRCA2 germline mutations were identified in 14.17% (19/134) of the patients. Among 113 patients with strong family history for breast/ovarian cancer (HBOC), 18 (15.9%) were positive for heterozygous BRCA mutations (9 in BRCA1 and 9 in BRCA2). In the group of patients without evidence of HBOC (21 patients), only one patient (4.8%) with ovarian cancer (OC) carried the c.2338C > T (Gln780X) pathogenic BRCA1 mutation. Our study outlined 6 (31.7%) novel pathogenic BRCA mutations, according to the BIC and ClinVar databases. New BRCA1 mutations were c.4067-4071 delAAGAA, c.296_297delTG, c.3364_3370 dupACAGATT and c.4041_4042delAG. New BRCA2 mutations were c.1976_1800 delCTTAT, c.2095C > T and c.9097delA.

Conclusions

This study identified 6 novel mutations for BRCA1/BRCA2 genes (i.e. 31.7% of BRCA mutations) which indicate the necessity of NGS in patients with high risk of BOC in Tunisian patients. Our results will contribute in the implementation of genetic counseling and testing for families with high-risk of hereditary breast/ovarian cancer in Tunisia.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Local Habib Bourguiba Committee.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.