Next-generation sequencing in familial breast cancer patients from Lebanon

Nadine Jalkh, Eliane Chouery, Zahraa Haidar, Christina Khater, David Atallah, Hamad Mohamed Ali Yaseen, Makia J. Marafie, Mohamed R. Al-Mulla, Fahd Al-Mulla, Andre Megarbane

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number8
Pages (from-to)1-12
Number of pages12
JournalBMC Medical Genomics
Volume10
Issue number1
DOIs
Publication statusPublished - 15 Feb 2017

Keywords

  • BRCA
  • Breast cancer
  • Exome
  • Familial
  • Germline
  • Lebanon
  • Mutation
  • Next-generation sequencing

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