Next-generation sequencing in familial breast cancer patients from Lebanon.

Autor:	Jalkh N; Unité de Génétique Médicale, Pôle Technologie Santé, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon., Chouery E; Unité de Génétique Médicale, Pôle Technologie Santé, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon., Haidar Z; Unité de Génétique Médicale, Pôle Technologie Santé, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon., Khater C; Trad Hospital, Beirut, Lebanon., Atallah D; Department of Gynecology and Obstetrics, Hôtel-Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon., Ali H; Department of Medical Laboratory Sciences (MLS), Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Safat, Kuwait.; Dasman Diabetes Institute (DDI), P.O Box 1180, Dasman, 15462, Kuwait., Marafie MJ; Kuwait Medical Genetics Center, Maternity Hospital, Safat, Kuwait., Al-Mulla MR; Department of Computing Sciences and Engineering, Kuwait University, P.O. Box 5969, Safat, 13060, Kuwait., Al-Mulla F; Dasman Diabetes Institute (DDI), P.O Box 1180, Dasman, 15462, Kuwait. fahd@al-mulla.org.; Health Sciences Center, Faculty of Medicine, Department of Pathology, Kuwait University, P.O.Box 24923, Safat, 13110, Kuwait. fahd@al-mulla.org., Megarbane A; Institut Jerome Lejeune, Paris, France. andre.megarbane@yahoo.fr.
Jazyk:	angličtina
Zdroj:	BMC medical genomics [BMC Med Genomics] 2017 Feb 15; Vol. 10 (1), pp. 8. Date of Electronic Publication: 2017 Feb 15.
DOI:	10.1186/s12920-017-0244-7
Abstrakt:	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.
Databáze:	MEDLINE
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