Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing.

TitleDiscovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing.
Publication TypeJournal Article
Year of Publication2011
AuthorsPflueger D, Terry S, Sboner A, Habegger L, Esgueva R, Lin P-C, Svensson MA, Kitabayashi N, Moss BJ, MacDonald TY, Cao X, Barrette T, Tewari AK, Chee MS, Chinnaiyan AM, Rickman DS, Demichelis F, Gerstein MB, Rubin MA
JournalGenome Res
Date Published2011 Jan
KeywordsAntigens, CD, Antigens, CD9, Computational Biology, Cyclin-Dependent Kinase Inhibitor p21, Gene Expression Profiling, Gene Fusion, Humans, I-kappa B Kinase, In Situ Hybridization, Fluorescence, Male, Membrane Glycoproteins, Molecular Sequence Data, Prostatic Neoplasms, Proto-Oncogene Proteins c-ets, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Serine Endopeptidases, Trans-Activators

Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2-ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype.

Alternate JournalGenome Res.
PubMed ID21036922
PubMed Central IDPMC3012926
Grant ListR01-CA116337 / CA / NCI NIH HHS / United States
R01-CA125612 / CA / NCI NIH HHS / United States
R44HG004237 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States