Kim Jung, Yu Jindan
Division of Hematology/Oncology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Biochim Biophys Acta. 2012 Apr;1825(2):186-96. doi: 10.1016/j.bbcan.2011.12.003. Epub 2012 Jan 3.
Major breakthroughs at the beginning of this century in high-throughput technologies have profoundly transformed biological research. Significant knowledge has been gained regarding our biological system and its disease such as malignant transformation. In this review, we summarize leading discoveries in prostate cancer research derived from the use of high-throughput approaches powered by microarrays and massively parallel next-generation sequencing (NGS). These include the seminal discovery of chromosomal translocations such as TMPRSS2-ERG gene fusions as well as the identification of critical oncogenes exemplified by the polycomb group protein EZH2. We then demonstrate the power of interrogating genomic and epigenomic data in understanding the plethora of mechanisms of transcriptional regulation. As an example, we review how androgen receptor (AR) binding events are mediated at multiple levels through protein-DNA interaction, histone and DNA modifications, as well as high-order chromatin structural changes.
本世纪初高通量技术的重大突破深刻改变了生物学研究。我们对生物系统及其疾病（如恶性转化）已有了大量认识。在本综述中，我们总结了前列腺癌研究中的主要发现，这些发现源自使用由微阵列和大规模平行下一代测序（NGS）驱动的高通量方法。其中包括诸如TMPRSS2-ERG基因融合等染色体易位的开创性发现，以及以多梳蛋白家族蛋白EZH2为代表的关键致癌基因的鉴定。然后，我们展示了在理解转录调控的众多机制方面，研究基因组和表观基因组数据的作用。例如，我们回顾了雄激素受体（AR）结合事件如何通过蛋白质-DNA相互作用、组蛋白和DNA修饰以及高阶染色质结构变化在多个层面上介导。
