Prostate Cancer Transcriptomic Subtypes

While the DNA of a tumor is often equated to a fingerprint or its unique genetic identify, a tumor's RNA profile represents a complex dynamic state more akin to a tumors personality or distinct behavior. Of the 11 types of RNA, the translational and clinical focus in prostate cancer has been primarily on mRNA and lncRNA. The most common use of RNA-based biomarkers is to assess a tumor's aggressiveness or treatment sensitivity. However, multiple gene expression signatures have been developed to capture the functional state that results from canonical DNA alterations, including ERG fusions, SPOP mutations, and Rb loss. More commonly, these biomarkers have been used to develop over 30 prognostic gene expression signatures, three of which are now commercially available and being increasingly incorporated into clinical trials. In parallel, the ability to use microarray and RNAseq technologies have allowed high throughput methods of performing whole transcriptomic analyses. This has enabled the discovery and training of numerous predictive biomarker signatures rooted in biologically informed pathways to determine which tumors are more sensitive or resistant to various treatments, including androgen-deprivation therapy, radiotherapy, chemotherapy, and PARP inhibition. This chapter will review the various types of RNA, technologies available to assess gene expression, and describe the available gene expression signatures for prostate cancer.