Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience

Abstract Background The incidence of breast cancer (BC) and ovarian cancer (OC) has increased in Saudi Arabia. The western region of Saudi Arabia presents a unique population with distinct genetic backgrounds, making it vital to investigate the prevalence of BC/OC-associated gene mutations in this a...

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Main Authors: Samar N. Ekram, Omima Elemam, Munzir Alandonisi, Arwa Flemban, Jamil Samkari, Hassan H. Zainuddin, Zohor Azher, Emad Tashkandi, Ahmad Mufti, Asim Khogeer
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Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02640-x
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author Samar N. Ekram
Omima Elemam
Munzir Alandonisi
Arwa Flemban
Jamil Samkari
Hassan H. Zainuddin
Zohor Azher
Emad Tashkandi
Ahmad Mufti
Asim Khogeer
author_facet Samar N. Ekram
Omima Elemam
Munzir Alandonisi
Arwa Flemban
Jamil Samkari
Hassan H. Zainuddin
Zohor Azher
Emad Tashkandi
Ahmad Mufti
Asim Khogeer
author_sort Samar N. Ekram
collection DOAJ
description Abstract Background The incidence of breast cancer (BC) and ovarian cancer (OC) has increased in Saudi Arabia. The western region of Saudi Arabia presents a unique population with distinct genetic backgrounds, making it vital to investigate the prevalence of BC/OC-associated gene mutations in this area. This study aimed to determine the prevalence and mutational profiles of BC and/or OC predisposing genes in the western region of Saudi Arabia, and to characterize the associated phenotypes in individuals carrying these mutations. Methods We employed next-generation sequencing (NGS) to identify the mutational spectra of 209 Saudi Arabian patients with BC and/or OC from the Western region. Results 51/209 (24.4%) patients had a mutation in one of the BC/OC predisposing genes. Overall, 34, 10, and 7 PV/LPV were identified in BRCA1, BRCA2, and other genes, respectively. Mutations in BRCA1 were predominant and strongly related to high-grade, triple-negative BC. BRCA1 NM_007294.4:c.1140dup p.(Lys381Glufs*3), NM_007294.4:c.5095C > T p.(Arg1699Trp), NM_007294.4:c.4986 + 6 T > C (p.?), NM_007294.4:c.5251C > T p.(Arg1751*), and NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs*3) were recurrent with NM_007294.4:c.3217_3218del p.(Gly1073*), NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs*3), and NM_007294.4:c.5234del p.(Asn1745Thrfs*20) being novel. The combined frequency of recurrent mutations in BRCA1 was 42%. Concerning BRCA2, we identified a recurrent variant NM_000059.4:c.7480C > T p.(Arg2494*) and two novel variants NM_000059.4:c.643del p.(Glu215Lysfs*15) and NM_000059.4: EXon1-8del. Conclusion In our study, we identified a high prevalence of BRCA1/2 variants in the western region of Saudi Arabia, offering novel and important insights specific to this area. We also identified other gene variants, though their impact remains unclear due to the limited sample size. This work represents an important first step in understanding the genetic factors contributing to breast and ovarian cancer in the Western region. It underscores the urgent need for larger studies to comprehensively explore the genetic landscape and better understand how these variants influence cancer risk in this population.
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spelling doaj-art-e6a75190080c4995b88db2f8de29d86a2025-08-20T01:53:23ZengSpringerDiscover Oncology2730-60112025-05-0116111510.1007/s12672-025-02640-xMutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experienceSamar N. Ekram0Omima Elemam1Munzir Alandonisi2Arwa Flemban3Jamil Samkari4Hassan H. Zainuddin5Zohor Azher6Emad Tashkandi7Ahmad Mufti8Asim Khogeer9Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura UniversityMedical Oncology, Oncology Centre, King Abdullah Medical CityMedical Oncology, Oncology Centre, King Abdullah Medical CityDepartment of Pathology, Faculty of Medicine, Umm Al-Qura UniversityFamily and Community Medicine Department, Faculty of Medicine in Rabigh, King Abdulaziz UniversityCollege of Medicine, Umm Al-Qura UniversityDepartment of Medical Genetics, Faculty of Medicine, Umm Al-Qura UniversityCollege of Medicine, Umm Al-Qura UniversityDepartment of Medical Genetics, Faculty of Medicine, Umm Al-Qura UniversityResearch Department, The Strategic Ministry Planning Administration, General Directorate of Health Affairs of Makkah Region, Ministry of HealthAbstract Background The incidence of breast cancer (BC) and ovarian cancer (OC) has increased in Saudi Arabia. The western region of Saudi Arabia presents a unique population with distinct genetic backgrounds, making it vital to investigate the prevalence of BC/OC-associated gene mutations in this area. This study aimed to determine the prevalence and mutational profiles of BC and/or OC predisposing genes in the western region of Saudi Arabia, and to characterize the associated phenotypes in individuals carrying these mutations. Methods We employed next-generation sequencing (NGS) to identify the mutational spectra of 209 Saudi Arabian patients with BC and/or OC from the Western region. Results 51/209 (24.4%) patients had a mutation in one of the BC/OC predisposing genes. Overall, 34, 10, and 7 PV/LPV were identified in BRCA1, BRCA2, and other genes, respectively. Mutations in BRCA1 were predominant and strongly related to high-grade, triple-negative BC. BRCA1 NM_007294.4:c.1140dup p.(Lys381Glufs*3), NM_007294.4:c.5095C > T p.(Arg1699Trp), NM_007294.4:c.4986 + 6 T > C (p.?), NM_007294.4:c.5251C > T p.(Arg1751*), and NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs*3) were recurrent with NM_007294.4:c.3217_3218del p.(Gly1073*), NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs*3), and NM_007294.4:c.5234del p.(Asn1745Thrfs*20) being novel. The combined frequency of recurrent mutations in BRCA1 was 42%. Concerning BRCA2, we identified a recurrent variant NM_000059.4:c.7480C > T p.(Arg2494*) and two novel variants NM_000059.4:c.643del p.(Glu215Lysfs*15) and NM_000059.4: EXon1-8del. Conclusion In our study, we identified a high prevalence of BRCA1/2 variants in the western region of Saudi Arabia, offering novel and important insights specific to this area. We also identified other gene variants, though their impact remains unclear due to the limited sample size. This work represents an important first step in understanding the genetic factors contributing to breast and ovarian cancer in the Western region. It underscores the urgent need for larger studies to comprehensively explore the genetic landscape and better understand how these variants influence cancer risk in this population.https://doi.org/10.1007/s12672-025-02640-xBreast cancerOvarian cancerNext-generation sequencingBRCA1BRCA2Germline mutation
spellingShingle Samar N. Ekram
Omima Elemam
Munzir Alandonisi
Arwa Flemban
Jamil Samkari
Hassan H. Zainuddin
Zohor Azher
Emad Tashkandi
Ahmad Mufti
Asim Khogeer
Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience
Discover Oncology
Breast cancer
Ovarian cancer
Next-generation sequencing
BRCA1
BRCA2
Germline mutation
title Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience
title_full Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience
title_fullStr Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience
title_full_unstemmed Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience
title_short Mutational spectrum and profile of breast and ovarian cancer patients in Saudi Arabia’s western region: single center experience
title_sort mutational spectrum and profile of breast and ovarian cancer patients in saudi arabia s western region single center experience
topic Breast cancer
Ovarian cancer
Next-generation sequencing
BRCA1
BRCA2
Germline mutation
url https://doi.org/10.1007/s12672-025-02640-x
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