Ekram Samar N, Elemam Omima, Alandonisi Munzir, Flemban Arwa, Samkari Jamil, Zainuddin Hassan H, Azher Zohor, Tashkandi Emad, Mufti Ahmad, Khogeer Asim
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 715, 21955, Makkah, Saudi Arabia.
Medical Oncology, Oncology Centre, King Abdullah Medical City, Makkah, Saudi Arabia.
Discov Oncol. 2025 May 20;16(1):829. doi: 10.1007/s12672-025-02640-x.
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.
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.
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.(Lys381Glufs3), 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.(Met1689Ilefs3) were recurrent with NM_007294.4:c.3217_3218del p.(Gly1073), NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs3), and NM_007294.4:c.5234del p.(Asn1745Thrfs20) 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.
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.
沙特阿拉伯乳腺癌（BC）和卵巢癌（OC）的发病率有所上升。沙特阿拉伯西部地区的人群具有独特的遗传背景，因此调查该地区BC/OC相关基因突变的患病率至关重要。本研究旨在确定沙特阿拉伯西部地区BC和/或OC易感基因的患病率和突变谱，并对携带这些突变的个体的相关表型进行特征分析。
我们采用下一代测序（NGS）技术来识别209名来自沙特阿拉伯西部地区的BC和/或OC患者的突变谱。
51/209（24.4%）的患者在BC/OC易感基因之一中存在突变。总体而言，分别在BRCA1、BRCA2和其他基因中鉴定出34、10和7个致病性/可能致病性变异。BRCA1突变占主导地位，且与高级别三阴性乳腺癌密切相关。BRCA1 NM_007294.4:c.1140dup p.(Lys381Glufs3)、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)和NM_007294.4:c.5067_5074+1del p.(Met1689Ilefs3)为常见突变，而NM_007294.4:c.3217_3218del p.(Gly1073)、NM_007294.4:c.5067_5074+1del p.(Met1689Ilefs3)和NM_007294.4:c.5234del p.(Asn1745Thrfs20)为新发现的突变。BRCA1中常见突变的合并频率为42%。关于BRCA2，我们鉴定出一个常见变异NM_000059.4:c.7480C>T p.(Arg2494*)和两个新变异NM_000059.4:c.643del p.(Glu215Lysfs*15)以及NM_000059.4: EXon1-8del。
在我们的研究中，我们发现沙特阿拉伯西部地区BRCA1/2变异的患病率很高，为该地区提供了新的重要见解。我们还鉴定出了其他基因变异，不过由于样本量有限，它们的影响尚不清楚。这项工作是了解沙特阿拉伯西部地区乳腺癌和卵巢癌遗传因素的重要第一步。它强调了迫切需要开展更大规模的研究，以全面探索该地区的遗传格局，并更好地了解这些变异如何影响该人群的癌症风险。
