All authors: Memorial Sloan-Kettering Cancer Center; Zsofia K. Stadler, Mark E. Robson, and Kenneth Offit, Weill Cornell Medical College, New York, NY.
J Clin Oncol. 2014 Mar 1;32(7):687-98. doi: 10.1200/JCO.2013.49.7271. Epub 2014 Jan 21.
Next-generation sequencing (NGS) has enabled whole-exome and whole-genome sequencing of tumors for causative mutations, allowing for more accurate targeting of therapies. In the process of sequencing the tumor, comparisons to the germline genome may identify variants associated with susceptibility to cancer as well as other hereditary diseases. Already, the combination of massively parallel sequencing and selective capture approaches has facilitated efficient simultaneous genetic analysis (multiplex testing) of large numbers of candidate genes. As the field of oncology incorporates NGS approaches into tumor and germline analyses, it has become clear that the ability to achieve high-throughput genotyping surpasses our current ability to interpret and appropriately apply the vast amounts of data generated from such technologies. A review of the current state of knowledge of rare and common genetic variants associated with cancer risk or treatment outcome reveals significant progress, as well as a number of challenges associated with the clinical translation of these discoveries. The combined efforts of oncologists, genetic counselors, and cancer geneticists will be required to drive the paradigm shift toward personalized or precision medicine and to ensure the incorporation of NGS technologies into the practice of preventive oncology.
下一代测序（NGS）已经实现了肿瘤的外显子组和全基因组测序，以寻找致病突变，从而更准确地靶向治疗。在对肿瘤进行测序的过程中，与种系基因组的比较可能会识别出与癌症易感性以及其他遗传性疾病相关的变体。已经，大规模平行测序和选择性捕获方法的结合促进了大量候选基因的高效同时遗传分析（多重测试）。随着肿瘤学领域将 NGS 方法纳入肿瘤和种系分析，很明显，实现高通量基因分型的能力超过了我们目前解释和适当应用这些技术产生的大量数据的能力。对与癌症风险或治疗结果相关的罕见和常见遗传变异的当前知识状态的审查揭示了重大进展，以及与这些发现的临床转化相关的一些挑战。肿瘤学家、遗传咨询师和癌症遗传学家的共同努力将需要推动向个性化或精准医学的范式转变，并确保将 NGS 技术纳入预防肿瘤学的实践。
