Abstract
BackgroundFamilial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16–40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature.MethodsIn the presented study, 45 Lebanese patients with a reported family history of BC were tested using Whole Exome Sequencing (WES) technique followed by Sanger sequencing validation.ResultsNineteen pathogenic mutations were identified in this study. These 19 mutations were found in 13 different genes such as: ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53.ConclusionsIn this first application of WES on BC in Lebanon, we detected six BRCA1 and BRCA2 deleterious mutations in seven patients, with a total prevalence of 15.5%, a figure that is lower than those reported in the Western literature. The p.C44F mutation in the BRCA1 gene appeared twice in this study, suggesting a founder effect. Importantly, the overall mutation prevalence was equal to 40%, justifying the urgent need to deploy WES for the identification of genetic variants responsible for familial BC in the Lebanese population.
Highlights
Familial breast cancer (BC) represents 5 to 10% of all BC cases
While mutations in BRCA1 and BRCA2 genes explain 16–40% of all familial BC cases [1,2,3], other genes have been found to increase BC susceptibility, which highlights the polygenic nature of many BC cases [4]
We identified, in 45 patients with familial BC, 19 pathogenic mutations that are disease causing mutations (DM) mutations according to the HGMD Professional database (Table 2)
Summary
Familial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16–40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. While mutations in BRCA1 and BRCA2 genes explain 16–40% of all familial BC cases [1,2,3], other genes have been found to increase BC susceptibility, which highlights the polygenic nature of many BC cases [4]. Some of these genes including CDH1, TP53, PTEN and STK11, less frequently altered compared to the BRCA1/2 genes, they have been linked to high-penetrance autosomal dominant BC [5,6,7]. These genes include the Fanconi anemia pathway genes: FANCA, PALB2, BRIP1, RAD51C and XRCC2
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