Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
Annu Rev Genomics Hum Genet. 2017 Aug 31;18:201-227. doi: 10.1146/annurev-genom-091416-035305. Epub 2017 May 15.
Next-generation or massively parallel sequencing has transformed the landscape of genetic testing for cancer susceptibility. Panel-based genetic tests evaluate multiple genes simultaneously and rapidly. Because these tests are frequently offered in clinical settings, understanding their clinical validity and utility is critical. When evaluating the inherited risk of breast and ovarian cancers, panel-based tests provide incremental benefit compared with BRCA1/2 genetic testing. For inherited risk of other cancers, such as colon cancer and pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based testing are higher; in fact, simultaneous evaluation of multiple genes has been the historical standard for these diseases. Evaluating inherited risk with panel-based testing has recently entered clinical practice for prostate and pancreatic cancers, with potential therapeutic implications. The resulting variants of uncertain significance and mutations with unclear actionability pose challenges to service providers and patients, underscoring the importance of genetic counseling and data-sharing initiatives. This review explores the evolving merits, challenges, and nuances of panel-based testing for cancer susceptibility.
下一代或大规模平行测序改变了癌症易感性的基因检测格局。基于面板的基因检测同时快速评估多个基因。由于这些测试经常在临床环境中提供,因此了解其临床有效性和实用性至关重要。在评估乳腺癌和卵巢癌的遗传风险时,与 BRCA1/2 基因检测相比,基于面板的测试提供了额外的益处。对于其他癌症(如结肠癌和嗜铬细胞瘤-副神经节瘤)的遗传风险,基于面板的测试具有更高的临床实用性和收益;实际上,同时评估多个基因一直是这些疾病的历史标准。基于面板的测试评估遗传性风险最近已进入前列腺癌和胰腺癌的临床实践,具有潜在的治疗意义。不确定意义的变体和作用机制不明的突变对服务提供商和患者构成了挑战,突显了遗传咨询和数据共享计划的重要性。这篇综述探讨了基于面板的癌症易感性检测的不断发展的优点、挑战和细微差别。