Wu H, Wu X, Liang Z
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Gene Ther. 2017 Oct;24(10):601-609. doi: 10.1038/gt.2017.73. Epub 2017 Aug 3.
The BRCA1/2 genes are long and complex and mutation carriers are at risk of developing malignancies, mainly of gynecological origin. Various mutations arise in these genes and their characterization is a time-consuming, cost intensive, complicated process. Tumors of BRCA1/2 origin have distinct molecular and histological features that can impact responses to therapy. Therefore, detection of these mutations constitutes an important step in the risk assessment, prevention strategy and treatment of subjects. Although Sanger sequencing is the gold standard for the detection of genetic mutations, several next generation sequencing-based high throughput platforms have been developed and adapted for the detection of BRCA1/2 mutations. This review provides a comprehensive overview of the sequencing platforms available for the screening and identification of these mutations. We also summarize what is known about the different types of mutations that arise in these genes and the tumor spectra they result in. Finally, we present a short discussion on existing clinical guidelines which assist physicians in the decision-making process. These parameters have important consequences for the management of patients and an urgent need exists for the development of detection platforms that are cost effective and can provide clinicians with conclusive results within a significantly shorter time.
BRCA1/2基因冗长且复杂，突变携带者有发生恶性肿瘤的风险，主要是妇科来源的恶性肿瘤。这些基因会出现各种突变，对其进行特征鉴定是一个耗时、成本高昂且复杂的过程。源自BRCA1/2的肿瘤具有独特的分子和组织学特征，可能会影响治疗反应。因此，检测这些突变是对受试者进行风险评估、预防策略制定和治疗的重要一步。虽然桑格测序是检测基因突变的金标准，但已经开发并采用了几种基于新一代测序的高通量平台来检测BRCA1/2突变。本综述全面概述了可用于筛查和鉴定这些突变的测序平台。我们还总结了关于这些基因中出现的不同类型突变及其所导致的肿瘤谱的已知信息。最后，我们简要讨论了有助于医生进行决策的现有临床指南。这些参数对患者管理具有重要影响，迫切需要开发具有成本效益且能在显著更短时间内为临床医生提供确定性结果的检测平台。
