Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030; email:
Annu Rev Med. 2014;65:33-48. doi: 10.1146/annurev-med-120811-171056. Epub 2013 Nov 21.
For a decade, the technologies behind DNA sequencing have improved rapidly in cost reduction and speed. Sequencing in large populations of cancer patients is leading to dramatic advances in our understanding of the cancer genome. The wide variety of cancer types sequenced and analyzed using these technologies has revealed many novel fundamental genetic mechanisms driving cancer initiation, progression, and maintenance. We have deepened our understanding of the signaling pathways, demonstrating disruption in epigenetic regulation and destabilization of the splicing machinery. The molecular mechanisms of resistance to targeted therapies are being elucidated for the first time. The translation of genome-scale variation into clinically actionable information is still in its infancy; nevertheless, insights from sequencing studies have led to the discovery of a variety of novel diagnostic biomarkers and therapeutic targets. Here, we review recent advances in cancer genomics and discuss what the new findings have taught us about cancer biology and, more importantly, how these new findings guide more effective diagnostic and treatment strategies.
十年来，DNA 测序技术在成本降低和速度提升方面取得了飞速发展。对大量癌症患者进行测序正在使我们对癌症基因组的理解取得显著进步。利用这些技术对各种类型的癌症进行测序和分析，揭示了许多驱动癌症发生、进展和维持的新的基本遗传机制。我们加深了对信号通路的理解，证明了表观遗传调控的中断和剪接机制的不稳定。靶向治疗耐药的分子机制正在首次被阐明。将基因组规模的变异转化为临床可操作的信息仍处于起步阶段；然而，测序研究的结果导致了多种新型诊断生物标志物和治疗靶点的发现。在这里，我们综述了癌症基因组学的最新进展，并讨论了新发现使我们对癌症生物学有了哪些了解，更重要的是，这些新发现如何指导更有效的诊断和治疗策略。
