Breast Cancer Research and Treatment

, Volume 168, Issue 3, pp 695–702 | Cite as

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

  • Al-Joharah Alhuqail
  • Areej Alzahrani
  • Hannah Almubarak
  • Sarah Al-Qadheeb
  • Lamyaa Alghofaili
  • Nisreen Almoghrabi
  • Hamed Alhussaini
  • Ben Ho Park
  • Dilek Colak
  • Bedri KarakasEmail author



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.


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.


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.


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.


Germline mutations Breast cancer Ovarian cancer BRCA1 BRCA2 Next-generation sequencing 



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.

Authors’ contribution

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.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

10549_2017_4635_MOESM1_ESM.docx (1.5 mb)
Supplementary material 1 (DOCX 1564 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Al-Joharah Alhuqail
    • 1
  • Areej Alzahrani
    • 1
  • Hannah Almubarak
    • 1
  • Sarah Al-Qadheeb
    • 1
  • Lamyaa Alghofaili
    • 2
  • Nisreen Almoghrabi
    • 1
  • Hamed Alhussaini
    • 3
  • Ben Ho Park
    • 4
  • Dilek Colak
    • 5
  • Bedri Karakas
    • 1
    Email author
  1. 1.Department of Molecular OncologyKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia
  2. 2.Alfaisal University Medical SchoolRiyadhSaudi Arabia
  3. 3.Department of OncologyKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia
  4. 4.The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA
  5. 5.Biostatistics, Epidemiology and Scientific ComputingKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia

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