Al-Joharah Alhuqail1, Areej Alzahrani1, Hannah Almubarak1, Sarah Al-Qadheeb1, Lamyaa Alghofaili2, Nisreen Almoghrabi1, Hamed Alhussaini3, Ben Ho Park4, Dilek Colak5, Bedri Karakas6. 1. Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, PO Box: 3354, Riyadh, 11211, Saudi Arabia. 2. Alfaisal University Medical School, Riyadh, 1153, Saudi Arabia. 3. Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia. 4. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287, USA. 5. Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia. 6. Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, PO Box: 3354, Riyadh, 11211, Saudi Arabia. bkarakas@kfshrc.edu.sa.
Abstract
PURPOSE: The BRCA1 and BRCA2 (BRCA) genes are heavily involved in mammalian cell DNA repair processes. Germline pathogenic mutations in BRCA increase the lifetime risk of developing breast and/or ovarian cancer in women. In the Arabian Peninsula, most breast and ovarian cancers are diagnosed as early-onset cases, some of which may be due to germline variants in BRCA genes. To identify the BRCA germline mutation frequency and spectrum in the Arab breast and ovarian cancers, we have sequenced the protein-coding exons of these genes. METHODS: All BRCA coding exons were sequenced using genomic DNA isolated from lymphocytes in 173 Arab breast and ovarian cancer patients by a massively parallel sequencing technology and verified by Sanger sequencing. RESULTS: We identified a total of 17 distinct pathogenic mutations, of which four were novel, in 28 patients; nine out of 108 breast (8.3%) and 19 out of 65 ovarian cancer (29.2%) patients. Thirteen of the 17 mutations were detected in BRCA1 and four mutations were found in BRCA2 gene. Four pathogenic BRCA1 mutations (c.1140dupG, c.4136_4137delCT, c.5095C>T, and c.5530delC) accounted for 54% of all the mutations detected in our patient cohort. Additionally, we identified a likely pathogenic BRCA1 missense variant in two of 108 breast (1.9%) and a BRCA2 missense variant in one of 65 ovarian cancer (1.5%) patients. CONCLUSIONS: The overall frequencies of the BRCA germline mutations were 10.2% in breast and 30.7% in ovarian cancer patients. These data shed new light into the prevalence of BRCA mutations in the Arab women population.
PURPOSE: The BRCA1 and BRCA2 (BRCA) genes are heavily involved in mammalian cell DNA repair processes. Germline pathogenic mutations in BRCA increase the lifetime risk of developing breast and/or ovarian cancer in women. In the Arabian Peninsula, most breast and ovarian cancers are diagnosed as early-onset cases, some of which may be due to germline variants in BRCA genes. To identify the BRCA germline mutation frequency and spectrum in the Arab breast and ovarian cancers, we have sequenced the protein-coding exons of these genes. METHODS: All BRCA coding exons were sequenced using genomic DNA isolated from lymphocytes in 173 Arab breast and ovarian cancerpatients by a massively parallel sequencing technology and verified by Sanger sequencing. RESULTS: We identified a total of 17 distinct pathogenic mutations, of which four were novel, in 28 patients; nine out of 108 breast (8.3%) and 19 out of 65 ovarian cancer (29.2%) patients. Thirteen of the 17 mutations were detected in BRCA1 and four mutations were found in BRCA2 gene. Four pathogenic BRCA1 mutations (c.1140dupG, c.4136_4137delCT, c.5095C>T, and c.5530delC) accounted for 54% of all the mutations detected in our patient cohort. Additionally, we identified a likely pathogenic BRCA1 missense variant in two of 108 breast (1.9%) and a BRCA2 missense variant in one of 65 ovarian cancer (1.5%) patients. CONCLUSIONS: The overall frequencies of the BRCA germline mutations were 10.2% in breast and 30.7% in ovarian cancerpatients. These data shed new light into the prevalence of BRCA mutations in the Arab women population.
Entities:
Keywords:
BRCA1; BRCA2; Breast cancer; Germline mutations; Next-generation sequencing; Ovarian cancer
Authors: George U Eleje; Ahizechukwu C Eke; Ifeanyichukwu U Ezebialu; Joseph I Ikechebelu; Emmanuel O Ugwu; Onyinye O Okonkwo Journal: Cochrane Database Syst Rev Date: 2018-08-24