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BMC Genomics

Open Access

Detection of rare single nucleotide variants affecting genes in the DNA repair pathways in hereditary breast cancer

  • Shireen Hussein1,
  • Adnan Merdad2,
  • Jaudah Al-Maghrabi3,
  • Mamdooh A. Gari1,
  • Fatma Al-Thubaiti2,
  • Ibtessam R. Hussein1,
  • Adeel G. Chaudhary1,
  • Adel M. Abuzenadah1,
  • Hanaa Tashkandi2,
  • Shadi Al-Khayyat4,
  • Taha Kumosani5,
  • Mohammed H. Al-Qahtani1 and
  • Ashraf Dallol1Email author
BMC Genomics201415(Suppl 2):P20

Published: 2 April 2014


Breast CancerBreast Cancer PatientPositive Family HistoryPersonalized MedicineExome Sequencing


Patients with hereditary breast cancer constitute a considerable fraction of overall breast cancer sufferers. The contribution of genetic factors to the development of breast cancer in the admixed and highly consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset [1]. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease.

Materials and methods

We have performed whole-exome sequencing of seven cases of breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform.


In addition to identifying two rare or novel mutations in BRCA2, we have identified several coding single nucleotide variations that affect genes controlling DNA repair in the BRCA1/2 pathway. The disruption of these pathways is very likely to contribute to breast cancer susceptibility.


Our findings suggest that whole exome sequencing is a powerful tool for identifying mutations associated with hereditary breast cancer that might be missed by using other classical genetic testing strategies. Moreover, this will guide the treatment of breast cancer patients who have failed to respond to first-line therapies, thus, it is a great leap towards applying personalized medicine in Saudi Arabia.

This project is partly funded by NSTIP grant 09-BIO-818-03.

Authors’ Affiliations

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
Department of Surgery, King Abdulaziz University Hospital, Kingdom of Saudi Arabia
Department of Pathology, King Abdulaziz University Hospital, Kingdom of Saudi Arabia
Department of Oncology, King Abdulaziz University Hospital, Kingdom of Saudi Arabia
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Kingdom of Saudi Arabia


  1. Mahboubi E: Epidemiology of cancer in Saudi Arabia, 1975–1985. Ann Saudi Med. 1987, 7: 265-276.Google Scholar


© Hussein et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.