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.
Highlights
Prostate cancer is world-wide the second most frequently diagnosed cancer type and the sixth leading cause of cancer-related death in men [1]
We carried out a comprehensive survey of fusion transcripts in RNA-sequencing data from 44 pairs of prostate cancer and benign tissues being sequenced by the The Cancer Genome Atlas (TCGA) consortium [3]
Thirteen novel recurrent fusion transcripts were nominated using stringent filtering criteria. These chimeras are characterized by having partner genes which are localized less than 60 kb apart and are transcribed from the same strand (10/13 gene pairs)
Summary
Prostate cancer is world-wide the second most frequently diagnosed cancer type and the sixth leading cause of cancer-related death in men [1]. Several discoveries of genetic alterations and gene expression abnormalities have revealed important molecular understanding to prostate cancer development and progression [2,3,4,5]. One predominant finding is the common expression of fusion genes in prostate cancer [5,6,7]. The most well-known is the fusion between TMPRSS2 and ERG, which are present in nearly half of the prostate cancers [5]. A number of common fusion transcripts generated from chromosomal rearrangements (e.g. translocation, insertion, deletion and inversion) have been detected by application of various high-throughput technologies [3, 4, 12,13,14,15]
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