ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1679528
Whole-Exome Sequencing in Saudi Colorectal Cancer Patients Reveals Distinct Mutational Patterns and Population Specific Pathogenic Variants
Provisionally accepted
Hanan E Alatwi1*
Amnah A Alharbi2
Rashid Mir3
Othman Alzahrani1
Abdulrahman H Alessa1
Yousef MohammedRabaa Hawsawi4,5Mohammed Ali Arishi6Aziz Dhaher Albalawi6- 1Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
- 2Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
- 3Department of Medical Lab Technology, Faculty of Applied Medical Sciences, and Prince Fahd Sultan Research chair for biomedical Research, University of Tabuk, Tabuk, Saudi Arabia
- 4King Faisal Specialist Hospital & Research Centre - Jeddah, Jeddah, Saudi Arabia
- 5Department of Biochemistry & Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- 6King Khaled Hospital, Faculty of laboratory, Ministry of health, Tabuk, Saudi Arabia
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Background: Colorectal cancer (CRC) shows significant inter-population heterogeneity in its genomic landscape, yet Middle Eastern populations are underrepresented in large-scale sequencing studies. This exploratory study aims to characterize somatic mutations and disrupted signaling pathways in Saudi Arabian CRC patients. Methods: We performed whole-exome sequencing (WES) on tumor DNA from 24 Saudi CRC patients. Somatic variants were identified and analyzed in a curated panel of cancer-related genes. Comparative analysis was conducted against The Cancer Genome Atlas colorectal cancer dataset (TCGA-COADREAD), and pathway enrichment analysis was performed. Results: Somatic variants were identified in 23 tumors, with recurrent mutations in BRCA2 (61%), TCF7L2 (52%), EGFR (43%), and SOS1 (43%). Compared to TCGA-COADREAD, mutation frequencies were significantly higher in BRCA2, EGFR, SLC25A5, and PIK3R2 (adjusted p < 0.0001). Among 258 total variants, 43% were novel, and 25 were classified as pathogenic, likely pathogenic, or deleterious, including 13 novel variants across nine genes. Pathway analysis revealed frequent disruptions in WNT/β-catenin (65%), homologous recombination (61%), PI3K (48%), and RTK/RAS (43%) signaling pathways. Conclusion: Our results reveal a distinct mutational profile in Saudi CRC patients, characterized by novel and enriched somatic variants affecting key oncogenic pathways. These findings underscore the necessity of including underrepresented populations in cancer genomics to support globally equitable precision oncology.
Keywords: colorectal cancer, Saudi cohort, Whole-exome sequencing, somatic mutation, pathway analysis, precision oncology
Received: 04 Aug 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Alatwi, Alharbi, Mir, Alzahrani, Alessa, Hawsawi, Arishi and Albalawi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hanan E Alatwi, h_alatwi@ut.edu.sa
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