Fawcett G L, Karina Eterovic A
Institute for Personalized Cancer Therapy (IPCT) at University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
Institute for Personalized Cancer Therapy (IPCT) at University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
Adv Clin Chem. 2017;78:123-162. doi: 10.1016/bs.acc.2016.07.006. Epub 2016 Aug 21.
The perfect method to discover and validate actionable somatic variants in cancer has not yet been developed, yet significant progress has been made toward this goal. There have been huge increases in the throughput and cost of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing technologies that have led to the burgeoning possibility of using sequencing data in clinical settings. Discovery of somatic mutations is relatively simple and has been improved recently due to laboratory methods optimization, bioinformatics algorithms development, and the expansion of various databases of population genomic information. Tiered systems of evidence evaluation are currently being used to classify genomic variants for clinicians to more rapidly and accurately determine actionability of these aberrations. These efforts are complicated by the intricacies of communicating sequencing results to physicians and supporting its biological relevance, emphasizing the need for increasing education of clinicians and administrators, and the ongoing development of ethical standards for dealing with incidental results. This chapter will focus on general aspects of DNA and RNA tumor sequencing technologies, data analysis and interpretation, assessment of biological and clinical relevance of genomic aberrations, ethical aspects of germline sequencing, and how these factors impact cancer personalized care.
尚未开发出用于发现和验证癌症中可操作的体细胞变异的完美方法，但在实现这一目标方面已取得重大进展。脱氧核糖核酸（DNA）和核糖核酸（RNA）测序技术的通量和成本大幅提高，使得在临床环境中使用测序数据的可能性迅速增加。体细胞突变的发现相对简单，并且由于实验室方法的优化、生物信息学算法的开发以及各种群体基因组信息数据库的扩展，近年来得到了改进。目前正在使用分层证据评估系统对基因组变异进行分类，以便临床医生能够更快、更准确地确定这些异常的可操作性。将测序结果传达给医生并支持其生物学相关性的复杂性使这些努力变得复杂，这强调了加强临床医生和管理人员教育的必要性，以及处理偶然结果的伦理标准的持续发展。本章将重点介绍DNA和RNA肿瘤测序技术的一般方面、数据分析与解读、基因组异常的生物学和临床相关性评估、种系测序的伦理方面，以及这些因素如何影响癌症个性化治疗。
