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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.

// Lina Cekaite 1,2 , Peter W. Eide 1,2 , Guro E. Lind 1,2 , Rolf I. Skotheim 1,2 and Ragnhild A. Lothe 1,2 1 Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway 2 K.G.Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway Correspondence to: Lina Cekaite, email: // Keywords : biomarker, colorectal neoplasm, miRNA, metastasis, target gene Received : August 17, 2015 Accepted : November 16, 2015 Published : November 25, 2015 Abstract Gene expression is in part regulated by microRNAs (miRNAs). This review summarizes the current knowledge of miRNAs in colorectal cancer (CRC); their role as growth regulators, the mechanisms that regulate the miRNAs themselves and the potential of miRNAs as biomarkers. Although thousands of tissue samples and bodily fluids from CRC patients have been investigated for biomarker potential of miRNAs (>160 papers presented in a comprehensive tables), none single miRNA nor miRNA expression signatures are in clinical use for this disease. More than 500 miRNA-target pairs have been identified in CRC and we discuss how these regulatory nodes interconnect and affect signaling pathways in CRC progression.

// Andreas M. Hoff 1, 2, 3, * , Bjarne Johannessen 1, 2, 3, * , Sharmini Alagaratnam 1, 2, 3 , Sen Zhao 1, 2, 3 , Torfinn Nome 1, 2, 3 , Marthe Lovf 1, 2, 3 , Anne C. Bakken 1, 2, 3 , Merete Hektoen 1, 2, 3 , Anita Sveen 1, 2, 3 , Ragnhild A. Lothe 1, 2, 3 , Rolf I. Skotheim 1, 2, 3 1 Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Norwegian Radium Hospital, Oslo, Norway 2 KG Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway 3 Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway * These authors have contributed equally to this work Correspondence to: Rolf I. Skotheim, e-mail: rolf.i.skotheim@rr-research.no Keywords: colorectal cancer, fusion genes, transcript variants, RACE-seq, splicing Received: July 01, 2015 Accepted: September 30, 2015 Published: October 12, 2015 ABSTRACT With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3′ parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2 - TCF7L2 , DHX35 - BPIFA2 and CASZ1 - MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7 , and a splice variant of S100A2 . Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets.