Research Papers:

Landscape of somatic mutations in breast cancer: new opportunities for targeted therapies in Saudi Arabian patients

Duna H. Barakeh, Rasha Aljelaify, Yara Bashawri, Amal Almutairi, Fatimah Alqubaishi, Mohammed Alnamnakani, Latifa Almubarak, Abdulrahman Al Naeem, Fatema Almushawah, May Alrashed and Malak Abedalthagafi _

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Oncotarget. 2021; 12:686-697. https://doi.org/10.18632/oncotarget.27909

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Duna H. Barakeh1, Rasha Aljelaify2, Yara Bashawri3, Amal Almutairi2, Fatimah Alqubaishi2, Mohammed Alnamnakani4, Latifa Almubarak2, Abdulrahman Al Naeem5, Fatema Almushawah6, May Alrashed7,8 and Malak Abedalthagafi2

1 Department of Pathology, King Saud University Medical City, Riyadh, Kingdom of Saudi Arabia

2 Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Kingdom of Saudi Arabia

3 Department of Biostatistics, Research Centre, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

4 Department of Pathology, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

5 Department of Radiology, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

6 Department of Surgery, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

7 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia

8 Chair of Medical and Molecular Genetics Research, King Saud University, Riyadh, Kingdom of Saudi Arabia

Correspondence to:

Malak Abedalthagafi,email: [email protected]

Keywords: breast cancer; PIK3CA; BCa; Saudi Arabia; BRCA

Received: November 17, 2020     Accepted: February 19, 2021     Published: March 30, 2021

Copyright: © 2021 Barakeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Breast cancer (BCa) ranks first in incidence rate among cancers in Arab females. The association between genetic polymorphisms in tumor suppressor genes and the risk of BCa has been studied in many ethnic populations with conflicting conclusions while Arab females and Saudi Arabian studies are still lacking. We screened a cohort of Saudi BCa patients by NGS using a bespoke gene panel to clarify the genetic landscape of this population, correlating and assessing genetic findings with clinical outcomes. We identified a total of 263 mutations spanning 51 genes, including several frequently mutated. Among the genes analyzed, the highest mutation rates were found in PIK3CA (12.9%), BRCA2 (11.7%), BRCA1 (10.2%), TP53 (6.0%), MSH2 (3.8%), PMS2 (3.8%), BARD1 (3.8%), MLH1 (3.4%), CDH1 (3.0%), RAD50 (3.0%), MSH6 (3.0%), NF1 (2.6%), in addition to others. We identified multiple common recurrent variants and previously reported mutations. We also identified 46 novel variants in 22 genes that were predicted to have a pathogenic effect. Survival analysis according to the four most common mutations (BRCA1, BRCA2, TP53, and PIK3CA) showed reduced survival in BRCA1 and BRCA2-mutant patients compared to total patients. Moreover, BRCA2 was demonstrated as an independent predictor of reduced survival using independent Cox proportional hazard models.

We reveal the landscape of the mutations associated with BCa in Saudi women, highlighting the importance of routine genetic sequencing in implementation of precision therapies in KSA.

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