Next-generation sequencing in familial breast cancer patients from Lebanon

• Published in: BMC medical genomics Vol. 10; no. 1; p. 8
• Main Authors: Jalkh, Nadine, Chouery, Eliane, Haidar, Zahraa, Khater, Christina, Atallah, David, Ali, Hamad, Marafie, Makia J, Al-Mulla, Mohamed R, Al-Mulla, Fahd, Megarbane, Andre
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.02.2017; BioMed Central
• Subjects: Adult; Aged; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - genetics; Cancer; Diagnosis; DNA Mutational Analysis; DNA sequencing; Female; Genetic aspects; Genetic Predisposition to Disease - genetics; Health aspects; High-Throughput Nucleotide Sequencing; Humans; Lebanon; Methods; Middle Aged; Mutation; Nucleotide sequencing; Lebanon; Exome; Lebanon; BRCA; Next-generation sequencing; Familial; Breast cancer; Mutation; Germline
• DOI: 10.1186/s12920-017-0244-7
• ISSN: 1755-8794

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. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature. In 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. Nineteen 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. In 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.