Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis
| العنوان: | Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
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| المؤلفون: | Khadija A.S. Al-Obaisi, Rong Bu, Fouad Al-Dayel, Shaham Beg, Mohsen Al Hazmi, Asma Tulbah, Khawla S. Al-Kuraya, Dahish Ajarim, Abdul K. Siraj |
| المصدر: | International Journal of Cancer |
| بيانات النشر: | John Wiley and Sons Inc., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, endocrine system diseases, DNA Mutational Analysis, 0302 clinical medicine, Risk Factors, Genotype, Prevalence, Age of Onset, skin and connective tissue diseases, Sanger sequencing, Genetics, education.field_of_study, BRCA1 Protein, Age Factors, Exons, Middle Aged, female genital diseases and pregnancy complications, Founder Effect, Oncology, 030220 oncology & carcinogenesis, symbols, Female, Adult, Population, Breast Neoplasms, Biology, Cancer Genetics and Epigenetics, 03 medical and health sciences, symbols.namesake, Middle East, Germline mutation, Breast cancer, breast cancer, BRCA 1, BRCA 2, medicine, Humans, Genetic Predisposition to Disease, education, Germ-Line Mutation, BRCA2 Protein, BRCA mutation, Haplotype, Sequence Analysis, DNA, medicine.disease, 030104 developmental biology, Haplotypes, Mutation, Founder effect |
| الوصف: | Ethnic differences of breast cancer genomics have prompted us to investigate the spectra of BRCA1 and BRCA2 mutations in different populations. The prevalence and effect of BRCA 1 and BRCA 2 mutations in Middle Eastern population is not fully explored. To characterize the prevalence of BRCA mutations in Middle Eastern breast cancer patients, BRCA mutation screening was performed in 818 unselected breast cancer patients using Capture and/or Sanger sequencing. 19 short tandem repeat (STR) markers were used for founder mutation analysis. In our study, nine different types of deleterious mutation were identified in 28 (3.4%) cases, 25 (89.3%) cases in BRCA 1 and 3 (10.7%) cases in BRCA 2. Seven recurrent mutations identified accounted for 92.9% (26/28) of all the mutant cases. Haplotype analysis was performed to confirm c.1140 dupG and c.4136_4137delCT mutations as novel putative founder mutation, accounting for 46.4% (13/28) of all BRCA mutant cases and 1.6% (13/818) of all the breast cancer cases, respectively. Moreover, BRCA 1 mutation was significantly associated with BRCA 1 protein expression loss (p = 0.0005). Our finding revealed that a substantial number of BRCA mutations were identified in clinically high risk breast cancer from Middle East region. Identification of the mutation spectrum, prevalence and founder effect in Middle Eastern population facilitates genetic counseling, risk assessment and development of cost‐effective screening strategy. What's new? Genetic testing for BRCA mutations reveals the ethnic diversity of prevalence and spectrum of BRCA1/BRCA2 mutations in breast cancer. Compared with other populations, however, little is known about ethnic differences in breast cancer genomics in populations in the Middle East region. Here, BRCA mutation screening was carried out in 818 Middle Eastern breast cancer patients. The authors identify two putative founder mutations—together accounting for more than 46% of BRCA cases—and a particular spectrum of deleterious BRCA mutations, which may be unique to the population. The findings could impact genetic counseling in Middle Eastern populations. |
| اللغة: | English |
| تدمد: | 1097-0215 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3849396fbcd9410a595acc6f0f37efaTest http://europepmc.org/articles/PMC5111783Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c3849396fbcd9410a595acc6f0f37efa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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