1Division of Human Genetics, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
J Natl Compr Canc Netw. 2021 Jan 6;19(1):103-108. doi: 10.6004/jnccn.2020.7674.
Historically, genetic testing (and billing) for hereditary cancer risk was essentially performed gene by gene, with clinicians ordering testing only for the genes most likely to explain a patient's or family's cancer presentation, with laboratories typically charging $1,000 to $1,500 for each gene that was sequenced. Given the expense, only patients at high risk of having a hereditary syndrome were offered testing. With the introduction of next-generation sequencing technologies, however, laboratories are able to test for multiple genes at the same time with greater efficiency, significantly decreased costs, and relatively little increased expense when adding additional genes. This has drastically altered clinical practice so that clinicians now typically order testing for a panel of multiple genes for most patients. Although this approach has streamlined the diagnostic odyssey, it has introduced several problems, as well, including difficulties in choosing the appropriate panel test for a given patient, assessing the significance of identified genetic variants (including variants of uncertain significance [VUS]), and understanding the disease risks and management associated with pathogenic variants in a given gene. Many laboratories offer testing for genes that have limited data supporting their associated cancer risks, which then leads to an inability to set management guidelines based on that gene. In addition, testing larger numbers of genes increases the likelihood of finding one or more VUS, which introduce their own management issues. Thus, although panel testing has certainly moved clinical practice forward in many ways, it has also raised its own set of problems that increase the complexity of genetic counseling and highlight the need for education of community practitioners on the complexities and nuances of this testing. Whenever possible, testing should be performed by, or in consultation with, cancer genetics professionals.
从历史上看，遗传性癌症风险的基因检测（和计费）基本上是逐个基因进行的，临床医生只为最有可能解释患者或家族癌症表现的基因进行检测，实验室通常对每个测序的基因收取 1000 到 1500 美元。鉴于费用高昂，只有患有遗传性综合征高风险的患者才会接受检测。然而，随着下一代测序技术的引入，实验室能够以更高的效率同时检测多个基因，成本显著降低，并且增加额外基因的费用相对较少。这极大地改变了临床实践，以至于现在临床医生通常会为大多数患者订购多个基因的面板检测。尽管这种方法简化了诊断过程，但也带来了一些问题，包括为特定患者选择适当的面板检测、评估已识别遗传变异的意义（包括意义不明的变异[VUS]）以及理解与特定基因中致病性变异相关的疾病风险和管理。许多实验室提供对具有有限数据支持其相关癌症风险的基因的检测，这导致无法根据该基因制定管理指南。此外，检测更多数量的基因增加了发现一个或多个 VUS 的可能性，这会带来自身的管理问题。因此，尽管面板检测在许多方面确实推动了临床实践的发展，但它也带来了一系列自身的问题，增加了遗传咨询的复杂性，并强调了对社区从业者进行该检测的复杂性和细微差别进行教育的必要性。只要有可能，就应由癌症遗传学专业人员进行或咨询检测。
