Khalifa Bin Zayed Institute for Personalized Cancer Therapy and Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; email:
Annu Rev Genomics Hum Genet. 2019 Aug 31;20:413-432. doi: 10.1146/annurev-genom-083118-015034. Epub 2019 Apr 17.
Since the discovery that DNA alterations initiate tumorigenesis, scientists and clinicians have been exploring ways to counter these changes with targeted therapeutics. The sequencing of tumor DNA was initially limited to highly actionable hot spots-areas of the genome that are frequently altered and have an approved matched therapy in a specific tumor type. Large-scale genome sequencing programs quickly developed technological improvements that enabled the deployment of whole-exome and whole-genome sequencing technologies at scale for pristine sample materials in research environments. However, the turning point for precision medicine in oncology was the innovations in clinical laboratories that improved turnaround time, depth of coverage, and the ability to reliably sequence archived, clinically available samples. Today, tumor genome sequencing no longer suffers from significant technical or financial hurdles, and the next opportunity for improvement lies in the optimal utilization of the technologies and data for many different tumor types.
自发现 DNA 改变引发肿瘤发生以来,科学家和临床医生一直在探索用靶向治疗来对抗这些变化的方法。肿瘤 DNA 的测序最初仅限于高度可操作的热点——基因组中经常发生改变的区域,并且在特定的肿瘤类型中有一种已批准的匹配疗法。大规模基因组测序计划迅速开发了技术改进,使全外显子组和全基因组测序技术能够在研究环境中对原始样本材料进行大规模部署。然而,肿瘤精准医学的转折点是临床实验室的创新,这些创新提高了周转时间、覆盖深度,以及可靠地对存档的、临床可用的样本进行测序的能力。如今,肿瘤基因组测序不再受到重大技术或财务障碍的困扰,下一个改进的机会在于为许多不同的肿瘤类型优化利用这些技术和数据。