Novel transcription-induced fusion RNAs in prostate cancer

Abstract

Prostate cancer is a clinically and pathologically heterogeneous disease with a broad spectrum of molecular abnormalities in the genome and transcriptome. One key feature is the involvement of chromosomal rearrangements creating fusion genes. Recent RNA-sequencing technology has uncovered that fusions which are not caused by chromosomal rearrangements, but rather meditated at transcription level, are common in both healthy and diseased cells. Such fusion transcripts have been proven highly associated with prostate cancer development and progression. To discover novel fusion transcripts, we analyzed RNA sequencing data from 44 primary prostate tumors and matched benign tissues from The Cancer Genome Atlas. Twenty-one high-confident candidates were significantly enriched in malignant vs. benign samples. Thirteen of the candidates have not previously been described in prostate cancer, and among them, five long intergenic non-coding RNAs are involved as fusion partners. Their expressions were validated in 50 additional prostate tumor samples and seven prostate cancer cell lines. For four fusion transcripts, we found a positive correlation between their expression and the expression of the 3′ partner gene. Among these, differential exon usage and qRT-PCR analyses in particular support that SLC45A3-ELK4 is mediated by an RNA polymerase read-through mechanism.