Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal Prostate Tissue

Abstract

Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessary to identify the criteria and features of fusion transcripts that are specific for cancer. In this review, we discuss optimization of RNA sequencing depth for fusion transcript discovery and the characteristics of fusion transcripts in normal prostate tissues and prostate cancer. We also propose a new classification of cancer-specific fusion transcripts on the basis of their tail gene fusion protein product and the roles that these fusions may play in cancer development.

Figure 1

Fusion transcripts in normal prostate tissues. A: Fusion transcripts result from continuous transcription of two contiguous genes. Schematic diagrams of TTTY15 and USP9Y genomes, fusion transcripts, and predicted translation products. Blue arrow indicates fusion breakpoint in the genome. Transcription direction is indicated by black arrow. Translation start site is indicated by 90° arrow. B: Fusion transcripts result from noncontiguous transcription. Schematic diagrams of MALAT1, WDR74, and TTN genomes, fusion transcripts, and predicted translation products. Blue arrow indicates fusion breakpoint in the genome. Transcription direction is indicated by black arrow. Translation start site is indicated by 90° arrow.

Figure 2

Schematic diagram of ERG activation. ERG protein is activated with phosphorylation of serine residues 81 and 215 by AKT kinase. The activated ERG protein facilitates the transcription of Wnt/LEF1, MMP9, and CXCR4.