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Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis
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 mutation...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111783/ https://www.ncbi.nlm.nih.gov/pubmed/27082205 http://dx.doi.org/10.1002/ijc.30143 |
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author | Bu, Rong Siraj, Abdul K. Al‐Obaisi, Khadija A.S. Beg, Shaham Al Hazmi, Mohsen Ajarim, Dahish Tulbah, Asma Al‐Dayel, Fouad Al‐Kuraya, Khawla S. |
author_facet | Bu, Rong Siraj, Abdul K. Al‐Obaisi, Khadija A.S. Beg, Shaham Al Hazmi, Mohsen Ajarim, Dahish Tulbah, Asma Al‐Dayel, Fouad Al‐Kuraya, Khawla S. |
author_sort | Bu, Rong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5111783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51117832016-11-16 Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis Bu, Rong Siraj, Abdul K. Al‐Obaisi, Khadija A.S. Beg, Shaham Al Hazmi, Mohsen Ajarim, Dahish Tulbah, Asma Al‐Dayel, Fouad Al‐Kuraya, Khawla S. Int J Cancer Cancer Genetics and Epigenetics 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. John Wiley and Sons Inc. 2016-05-03 2016-09-01 /pmc/articles/PMC5111783/ /pubmed/27082205 http://dx.doi.org/10.1002/ijc.30143 Text en © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Cancer Genetics and Epigenetics Bu, Rong Siraj, Abdul K. Al‐Obaisi, Khadija A.S. Beg, Shaham Al Hazmi, Mohsen Ajarim, Dahish Tulbah, Asma Al‐Dayel, Fouad Al‐Kuraya, Khawla S. Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
title | Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
title_full | Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
title_fullStr | Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
title_full_unstemmed | Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
title_short | Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis |
title_sort | identification of novel brca founder mutations in middle eastern breast cancer patients using capture and sanger sequencing analysis |
topic | Cancer Genetics and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111783/ https://www.ncbi.nlm.nih.gov/pubmed/27082205 http://dx.doi.org/10.1002/ijc.30143 |
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