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High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

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Acknowledgements

We thank the Research Center Administration for their continuous support. This project was supported by the Kingdom of Saudi Arabia National Science, Technology and Innovation Plan (NSTIP) Strategic Technologies in the Kingdom-Award No.: 12-BIO2947-2.

Author information

Authors and Affiliations

  1. Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, PO Box: 3354, Riyadh, 11211, Saudi Arabia

    Al-Joharah Alhuqail, Areej Alzahrani, Hannah Almubarak, Sarah Al-Qadheeb, Nisreen Almoghrabi & Bedri Karakas

  2. Alfaisal University Medical School, Riyadh, 1153, Saudi Arabia

    Lamyaa Alghofaili

  3. Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia

    Hamed Alhussaini

  4. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287, USA

    Ben Ho Park

  5. Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia

    Dilek Colak

Authors
  1. Al-Joharah Alhuqail
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  2. Areej Alzahrani
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  3. Hannah Almubarak
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  5. Lamyaa Alghofaili
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  7. Hamed Alhussaini
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  8. Ben Ho Park
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  10. Bedri Karakas
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Contributions

Study conception and design: BK and AJA. Methodology (DNA extraction, NGS and Sanger sequencing): BK, AJA, AA, and SA. Patient recruitment, sample, and clinical data collection: NA, HA, HA, and LA. Sequencing data analysis and interpretation: BK, DC, and BHP. Writing/editing the manuscript: BK and BHP. Overall supervision: BK.

Corresponding author

Correspondence to Bedri Karakas.

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The authors declare no competing financial interests.

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Alhuqail, AJ., Alzahrani, A., Almubarak, H. et al. High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients. Breast Cancer Res Treat 168, 695–702 (2018). https://doi.org/10.1007/s10549-017-4635-4

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  • DOI: https://doi.org/10.1007/s10549-017-4635-4

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