Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing
- Dorothee Pflueger1,12,
- Stéphane Terry1,12,
- Andrea Sboner2,3,12,
- Lukas Habegger3,
- Raquel Esgueva1,
- Pei-Chun Lin1,
- Maria A. Svensson1,
- Naoki Kitabayashi1,
- Benjamin J. Moss1,
- Theresa Y. MacDonald1,
- Xuhong Cao4,
- Terrence Barrette4,5,
- Ashutosh K. Tewari6,7,
- Mark S. Chee8,
- Arul M. Chinnaiyan4,5,9,
- David S. Rickman1,
- Francesca Demichelis1,10,
- Mark B. Gerstein2,3,11,13 and
- Mark A. Rubin1,13,14
- 1Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10021, USA;
- 2Molecular Biophysics and Biochemistry Department, Yale University, New Haven, Connecticut 06510, USA;
- 3Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06510, USA;
- 4Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 5Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 6Department of Urology, Weill Cornell Medical College, New York, New York 10021, USA;
- 7Institute of Prostate Cancer, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York 10021, USA;
- 8Prognosys Biosciences, Inc., La Jolla, California 92037, USA;
- 9Howard Hughes Medical Institute, Department of Urology, and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 10Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York 10021, USA;
- 11Department of Computer Science, Yale University, New Haven, Connecticut 06510, USA
-
↵12 These authors contributed equally to this work.
Abstract
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.
Footnotes
-
↵13 These authors shared senior authorship.
-
↵14 Corresponding author.
E-mail rubinma{at}med.cornell.edu; fax (212) 746-8816.
-
[Supplemental material is available online at http://www.genome.org. The data sets used in this study have been submitted to dbGaP (http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap) under accession no. phs000310.v1.p1. Sequences of the novel gene fusion transcripts from this study have been submitted to GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) under accession nos. HM245385–HM245396.]
-
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.110684.110.
- Received May 21, 2010.
- Accepted September 24, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
