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Cells
Volume 14
Issue 22
10.3390/cells14221791
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Somatic Mutation Profiling and Therapeutic Landscape of Breast Cancer in the MENA Region

by
Dinesh Velayutham
1,
Ramesh Elango
2,
Sameera Rashid
3,4,
Reem Al-Sarraf
3,
Mohammed Akhtar
3,
Khalid Ouararhni
5,
Puthen Veettil Jithesh
1 and
Nehad M. Alajez
1,2,*
1
College of Health & Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar
2
Translational Oncology Research Center (TORC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar
3
Department of Laboratory Medicine and Pathology (DLMP), Hamad Medical Corporation (HMC), Doha P.O. Box 34110, Qatar
4
National Health Service, Royal Liverpool University, Liverpool L7 8XP, UK
5
Genomics Core Facility, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar
*
Author to whom correspondence should be addressed.
Cells 2025, 14(22), 1791; https://doi.org/10.3390/cells14221791
Submission received: 18 September 2025 / Revised: 31 October 2025 / Accepted: 4 November 2025 / Published: 14 November 2025
(This article belongs to the Special Issue Molecular Mechanism and Therapeutic Opportunities of Breast Cancer)
Versions Notes

Abstract

Breast cancer remains a major global health challenge. Yet, genomic data from Middle Eastern and North African (MENA) populations are limited, restricting insights into disease drivers and therapeutic opportunities in this demographic. To address this gap, we performed whole-exome sequencing (WES) on 52 breast cancer samples, including 51 from the MENA region, to characterize somatic mutations and potential therapeutic targets. Across the cohort, 37,369 somatic variants matched entries in the COSMIC database, and driver prediction tools (BoostDM and OncodriveMUT) identified 2451 predicted driver mutations, including 648 known driver variants in genes such as TP53, PIK3CA, GATA3, PTEN, SF3B1, and KMT2C. In addition, 1803 novel predicted drivers were detected, many affecting DNA repair pathways, including homologous recombination (BRCA2, RAD51C), mismatch repair (MLH1, MSH2), and nucleotide excision repair (ERCC2, ERCC3), as well as regulators such as TP53 and ATM. Mutational signature analysis revealed a predominance of C>T substitutions and subtype-specific patterns, with SBS22 and SBS43 enriched in Luminal A tumors. Therapeutic annotation using OncoKB identified 223 actionable or likely oncogenic variants, highlighting potential targets for precision oncology. This study provides a comprehensive characterization of the breast cancer mutational landscape in MENA patients and offers a valuable resource for advancing genomic and therapeutic research in this demographic.
Keywords: breast cancer; somatic mutations; somatic signature; MENA region; Arab, driver mutations; therapeutic implications breast cancer; somatic mutations; somatic signature; MENA region; Arab, driver mutations; therapeutic implications

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MDPI and ACS Style

Velayutham, D.; Elango, R.; Rashid, S.; Al-Sarraf, R.; Akhtar, M.; Ouararhni, K.; Jithesh, P.V.; Alajez, N.M. Somatic Mutation Profiling and Therapeutic Landscape of Breast Cancer in the MENA Region. Cells 2025, 14, 1791. https://doi.org/10.3390/cells14221791

AMA Style

Velayutham D, Elango R, Rashid S, Al-Sarraf R, Akhtar M, Ouararhni K, Jithesh PV, Alajez NM. Somatic Mutation Profiling and Therapeutic Landscape of Breast Cancer in the MENA Region. Cells. 2025; 14(22):1791. https://doi.org/10.3390/cells14221791

Chicago/Turabian Style

Velayutham, Dinesh, Ramesh Elango, Sameera Rashid, Reem Al-Sarraf, Mohammed Akhtar, Khalid Ouararhni, Puthen Veettil Jithesh, and Nehad M. Alajez. 2025. "Somatic Mutation Profiling and Therapeutic Landscape of Breast Cancer in the MENA Region" Cells 14, no. 22: 1791. https://doi.org/10.3390/cells14221791

APA Style

Velayutham, D., Elango, R., Rashid, S., Al-Sarraf, R., Akhtar, M., Ouararhni, K., Jithesh, P. V., & Alajez, N. M. (2025). Somatic Mutation Profiling and Therapeutic Landscape of Breast Cancer in the MENA Region. Cells, 14(22), 1791. https://doi.org/10.3390/cells14221791

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