Shohdy K S, Kassem L, Elnahas T, Barsoum E M, Gabriel B, Elghazawy H, Lasheen S, Gourley C, Azim H A
School of Cancer Sciences and Cancer Research UK Scotland Institute, University of Glasgow, UK; Department of Clinical Oncology, Cairo University, Cairo, Egypt.
Department of Clinical Oncology, Cairo University, Cairo, Egypt.
ESMO Open. 2025 Jul 25;10(8):105510. doi: 10.1016/j.esmoop.2025.105510.
There is a lack of studies investigating the burden of BRCA1/2 pathogenic variants (PVs) in Northern African countries using next-generation sequencing (NGS)-based testing in patients with epithelial ovarian (EOC) and triple-negative breast cancer (TNBC).
We established a multicentre registry for genetic testing of unselected patients referred from five centres from 2019 to 2022 across Egypt. Germline or somatic BRCA1/2 sequencing was carried out by target enrichment using the AmoyDx® BRCA1/2 Mutation Kit, and sequencing was carried out using the Illumina NextSeq500 system.
Genetic testing was successfully carried out for 1349 of 1420 (95%) patients tested (EOC = 1031, TNBC = 318). The median age was 55 years (range 20-86 years). We identified 258 BRCA1/2 PVs affecting 254 (18.8%) patients. The rate of BRCA1/2 PVs in EOC and TNBC was 18.2% and 20.8%, respectively. Although the rate of PVs in our cohort was similar to the Western cancer population, there were significant differences in the enrichment at the variant level. The majority of recurrent BRCA2 PVs, but not BRCA1 PVs, were breast or ovarian lineage-unique. We developed a limited-resource conscious framework that provided a reclassification of 60% of identified variants of uncertain significance (VUS).
Our findings would help to enhance cancer care and enrich the genetic epidemiology of women from such understudied ancestries.
在北非国家，缺乏使用基于二代测序（NGS）的检测方法来研究上皮性卵巢癌（EOC）和三阴性乳腺癌（TNBC）患者中BRCA1/2致病变异（PVs）负担的研究。
我们建立了一个多中心登记处，用于对2019年至2022年期间从埃及五个中心转诊的未经选择的患者进行基因检测。使用厦门艾德生物科技股份有限公司的BRCA1/2突变检测试剂盒通过靶向富集进行胚系或体细胞BRCA1/2测序，并使用Illumina NextSeq500系统进行测序。
在1420名接受检测的患者中，成功对1349名（95%）患者进行了基因检测（EOC = 1031例，TNBC = 318例）。中位年龄为55岁（范围20 - 86岁）。我们鉴定出258个BRCA1/2 PVs，影响254名（18.8%）患者。EOC和TNBC中BRCA1/2 PVs的发生率分别为18.2%和20.8%。尽管我们队列中PVs的发生率与西方癌症人群相似，但在变异水平的富集方面存在显著差异。大多数复发性BRCA2 PVs（而非BRCA1 PVs）是乳腺或卵巢谱系特有的。我们开发了一个资源有限意识框架，对60%已鉴定的意义未明变异（VUS）进行了重新分类。
我们的研究结果将有助于加强癌症护理，并丰富来自此类研究不足的祖先群体的女性的遗传流行病学资料。
