title: Fusion transcript loci share many genomic features with non-fusion loci.
abstract: BACKGROUND
  Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies have shown extensively that these cells readily undergo fusion transcription.
  
  
  RESULTS
  We used the FusionMap program to identify high-confidence fusion transcripts from RNAseq data. The RNAseq datasets were from our (N = 8) and other (N = 14) clinical prostate tumors with adjacent non-cancer cells, and from the LNCaP prostate cancer cell line that were mock-, androgen- (DHT), and anti-androgen- (bicalutamide, enzalutamide) treated. In total, 185 fusion transcripts were identified from all RNAseq datasets. The majority (76%) of these fusion transcripts were 'read-through chimeras' derived from adjacent genes in the genome. Characterization of sequences at fusion loci were carried out using a combination of the FusionMap program, custom Perl scripts, and the RNAfold program. Our computational analysis indicated that most fusion junctions (76%) use the consensus GT-AG intron donor-acceptor splice site, and most fusion transcripts (85%) maintained the open reading frame. We assessed whether parental genes of fusion transcripts have the potential to form complementary base pairing between parental genes which might bring them into physical proximity. Our computational analysis of sequences flanking fusion junctions at parental loci indicate that these loci have a similar propensity as non-fusion loci to hybridize. The abundance of repetitive sequences at fusion and non-fusion loci was also investigated given that SINE repeats are involved in aberrant gene transcription. We found few instances of repetitive sequences at both fusion and non-fusion junctions. Finally, RT-qPCR was performed on RNA from both clinical prostate tumors and adjacent non-cancer cells (N = 7), and LNCaP cells treated as above to validate the expression of seven fusion transcripts and their respective parental genes. We reveal that fusion transcript expression is similar to the expression of parental genes.
  
  
  CONCLUSIONS
  Fusion transcripts maintain the open reading frame, and likely use the same transcriptional machinery as non-fusion transcripts as they share many genomic features at splice/fusion junctions.
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. j2.lai@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. j2.lai@qut.edu.au.|Current address: Genetic Technologies, 60-66 Hanover Street, Melbourne, Australia. j2.lai@qut.edu.au.
authors.forename: John
authors.initials: J
authors.lastname: Lai
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. J.an@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. J.an@qut.edu.au.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: An
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. i.seim@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. i.seim@qut.edu.au.|Comparative and Endocrine Biology Laboratory, Institute of Health and Biomedical Innovation, Brisbane, Australia. i.seim@qut.edu.au.|Ghrelin Research Group, Institute of Health and Biomedical Innovation, Brisbane, Australia. i.seim@qut.edu.au.
authors.forename: Inge
authors.initials: I
authors.lastname: Seim
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. c.walpole@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. c.walpole@qut.edu.au.
authors.forename: Carina
authors.initials: C
authors.lastname: Walpole
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. andrea.hoffman@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. andrea.hoffman@qut.edu.au.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hoffman
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. leire.moya@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. leire.moya@qut.edu.au.
authors.forename: Leire
authors.initials: L
authors.lastname: Moya
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. srilakshmi.srinivasan@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. srilakshmi.srinivasan@qut.edu.au.
authors.forename: Srilakshmi
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Anatomical Pathology, Pathology Queensland, Brisbane, Australia. Joanna_PerryKeene@health.qld.gov.au.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Perry-Keene
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. chenwei.wang@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. chenwei.wang@qut.edu.au.
authors.forename: Chenwei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. melanie.lehman@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. melanie.lehman@qut.edu.au.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Lehman
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. colleen.nelson@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. colleen.nelson@qut.edu.au.
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. j.clements@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. j.clements@qut.edu.au.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Clements
authors.affiliation: Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, Australia. jyotsna.batra@qut.edu.au.|Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. jyotsna.batra@qut.edu.au.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Batra
mesh_terms: D000728:Androgens / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D066264:Datasets as Topic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D059372:Nucleotide Motifs; D011471:Prostatic Neoplasms / Q000235:genetics*; D040641:Quantitative Trait Loci; D022821:RNA Splice Sites; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D022821:RNA Splice Sites