Al Ali Abeer Arif Abdalla Abutalib, Al Ali Moza Mohamed Alechleh, El-Shourbagy Dalia Mahmoud Abdel-Hamid, Tirmazy Syed Hammad Hassan, Mirza Imran, Raza Afsheen, Latif Muhammad Farooq, Yasaei Hemad
Dubai Genetics Center, Pathology and Genetics Department, Latifa Hospital, Dubai Academic Health Corporation, Dubai, United Arab Emirates.
Department of Oncology, Dubai Hospital, Dubai Academic Health Corporation, Dubai, United Arab Emirates.
J Cancer Res Clin Oncol. 2025 Apr 21;151(4):146. doi: 10.1007/s00432-025-06188-9.
Germline BRCA1/2 (gBRCA1/2) variants are strongly associated with hereditary cancers, and screening for these variants in high-risk populations is recommended for personalized management. This study aims to comprehensively characterize gBRCA1/2 variants in cancer and family screening cohorts from the Dubai Emirate, UAE.
A total of 443 patients with breast, ovarian, prostate and pancreatic cancer were tested for gBRCA1/2 variants from 2017 to 2022 using whole-gene sequencing, and data were analysed using variant interpretation and in-silico prediction tools. All BRCA1/2 variants were classified as P/LP or variants of uncertain significance (VUS) according to ACMG guidelines.
In the cancer cohort, 38 out of 306 patients harboured gBRCA1/2 P/LP or VUS variants. Of these, 23 (7.5%) were classified as BRCA1/2 P/LP, while 15 (4.9%) were categorized as VUS. These variants were predominantly observed in estrogen receptor-positive/progesterone receptor-positive (ER + /PR +) and triple-negative breast cancer patients. Common BRCA1 P/LP variants included deletion frameshift variants (c.4065_4068del, c.68_69delAG, c.3228_3229delAG), an insertion frameshift variant (c.1140dup), and a nonsense variant (c.5251C > T). BRCA2 P/LP variants included a nonsense variant (c.5645C > A), a missense variant (c.7007G > A), and a deletion frameshift variant (c.2254_2257del). In the family screening cohort, 14 out of 137 samples harboured BRCA1/2 P/LP orVUS. Of these, five (3.6%) were classified as P/LP, while nine (6.6%) were VUS. Pathogenic BRCA1 variants included deletions (c.4065_4068del, c.3756_3759del) and a nonsense variant (c.5095C > T), while BRCA2 PVs included a deletion frameshift (c.771_775del) and a novel missense variant (c.8377G > A). In both cohorts, novel distinct variants were observed.
gBRCA1/2 variant prevalence in cancer and family screening cohorts can serve as beneficial personalized tool for management and treatment of cancer patients. Larger studies from other emirates of UAE will serve as a foundation for robust risk assessment and implementation of treatment and prevention strategies.
种系BRCA1/2（gBRCA1/2）变异与遗传性癌症密切相关，建议在高危人群中筛查这些变异以进行个性化管理。本研究旨在全面描述阿联酋迪拜酋长国癌症和家族筛查队列中的gBRCA1/2变异。
2017年至2022年期间，共对443例乳腺癌、卵巢癌、前列腺癌和胰腺癌患者进行了gBRCA1/2变异检测，采用全基因测序，并使用变异解读和计算机预测工具进行数据分析。根据美国医学遗传学与基因组学学会（ACMG）指南，所有BRCA1/2变异被分类为致病性/可能致病性（P/LP）或意义未明变异（VUS）。
在癌症队列中，306例患者中有38例携带gBRCA1/2 P/LP或VUS变异。其中，23例（7.5%）被分类为BRCA1/2 P/LP，15例（4.9%）被分类为VUS。这些变异主要在雌激素受体阳性/孕激素受体阳性（ER+/PR+）和三阴性乳腺癌患者中观察到。常见的BRCA1 P/LP变异包括缺失移码变异（c.4065_4068del、c.68_69delAG、c.3228_3229delAG）、插入移码变异（c.1140dup）和无义变异（c.5251C>T）。BRCA2 P/LP变异包括无义变异（c.5645C>A）、错义变异（c.7007G>A）和缺失移码变异（c.2254_2257del）。在家族筛查队列中，137个样本中有14个携带BRCA1/2 P/LP或VUS。其中，5例（3.6%）被分类为P/LP，9例（6.6%）为VUS。致病性BRCA1变异包括缺失（c.4065_4068del、c.3756_3759del）和无义变异（c.5095C>T），而BRCA2致病性变异包括缺失移码（c.771_775del）和一个新的错义变异（c.8377G>A）。在两个队列中均观察到新的独特变异。
癌症和家族筛查队列中gBRCA1/2变异的患病率可作为癌症患者管理和治疗的有益个性化工具。来自阿联酋其他酋长国的更大规模研究将为有力的风险评估以及治疗和预防策略的实施奠定基础。
