Department of Medicine/Hematology and Oncology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.
Nat Rev Clin Oncol. 2012 Nov;9(11):621-30. doi: 10.1038/nrclinonc.2012.159. Epub 2012 Sep 11.
Massively parallel approaches to nucleic acid sequencing have matured from proof-of-concept to commercial products during the past 5 years. These technologies are now widely accessible, increasingly affordable, and have already exerted a transformative influence on the study of human cancer. Here, we review new features of cancer genomes that are being revealed by large-scale applications of these technologies. We focus on those insights most likely to affect future clinical practice. Foremost among these lessons, we summarize the formidable genetic heterogeneity within given cancer types that is appreciable with higher resolution profiling and larger sample sets. We discuss the inherent challenges of defining driving genomic events in a given cancer genome amidst thousands of other somatic events. Finally, we explore the organizational, regulatory and societal challenges impeding precision cancer medicine based on genomic profiling from assuming its place as standard-of-care.
在过去的 5 年中，大规模平行的核酸测序方法已经从概念验证发展到商业产品。这些技术现在已经广泛普及，价格也越来越实惠，并且已经对人类癌症的研究产生了变革性的影响。在这里，我们回顾了这些技术的大规模应用所揭示的癌症基因组的新特征。我们专注于那些最有可能影响未来临床实践的见解。其中最重要的是，我们总结了在更高分辨率的分析和更大的样本集中可以明显看到的给定癌症类型内存在的巨大遗传异质性。我们讨论了在给定的癌症基因组中定义驱动性基因组事件所面临的固有挑战，因为其中还存在着数千个其他的体细胞事件。最后，我们探讨了基于基因组分析的精准癌症医学在组织、监管和社会方面所面临的挑战，这些挑战阻碍了它成为标准治疗方法。
