Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center) and Medical Genetics Department of Medical Faculty, Adana, Turkey; InfoGenom, Cukurova Technopolis, Adana, Turkey.
Bursa Uludag University, Faculty of Medicine, Department of Medical Genetics, Bursa, Turkey.
Breast. 2022 Oct;65:15-22. doi: 10.1016/j.breast.2022.06.005. Epub 2022 Jun 21.
BRCA1/2 mutations play a significant role in cancer pathogenesis and predisposition particularly in breast, ovarian and prostate cancers. Thus, germline analysis of BRCA1 and BRCA2 is essential for clinical management strategies aiming at the identification of recurrent and novel mutations that could be used as a first screening approach. We analyzed germline variants of BRCA1/2 genes for 2168 individuals who had cancer diagnosis or high risk assessment due to BRCAs related cancers, referred to 10 health care centers distributed across 7 regions covering the Turkish landscape. Overall, 68 and 157 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-two novel variants were reported from both genes while BRCA2 showed higher mutational heterogeneity. We herein report the collective data as BRCA Turkish consortium that confirm the molecular heterogeneity in BRCAs among Turkish population, and also as the first study presenting the both geographical, demographical and gene based landscape of all recurrent and novel mutations which some might be a founder effect in comparison to global databases. This wider perspective leads to the most accurate variant interpretations which pave the way for the more precise and efficient management affecting the clinical and molecular aspects.
BRCA1/2 基因突变在癌症发病机制和易感性中起着重要作用，特别是在乳腺癌、卵巢癌和前列腺癌中。因此，对 BRCA1 和 BRCA2 的种系分析对于旨在识别可作为首次筛查方法的复发性和新突变的临床管理策略至关重要。我们分析了来自 2168 名个体的 BRCA1/2 基因的种系变异，这些个体因与 BRCA 相关的癌症而有癌症诊断或高风险评估，这些个体来自分布在覆盖土耳其景观的 7 个地区的 10 个医疗中心。总体而言，在 BRCA1 和 BRCA2 中分别鉴定出 68 和 157 个不同的突变。从这两个基因中报告了 22 个新变体，而 BRCA2 显示出更高的突变异质性。我们在此报告了 BRCA 土耳其联合研究的数据，这些数据证实了土耳其人群中 BRCA 中的分子异质性，也是首次在全球数据库中展示所有复发性和新突变的地理、人口和基因图谱，其中一些可能是一种起源效应。这种更广泛的视角导致了最准确的变异解释，为影响临床和分子方面的更精确和有效的管理铺平了道路。
