Interrogating genomic and epigenomic data to understand prostate cancer.

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.