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Letter
Nature 458, 97-101 (5 March 2009) | doi:10.1038/nature07638; Received 21 July 2008; Accepted 10 November 2008; Published online 11 January 2009
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Transcriptome sequencing to detect gene fusions in cancer
Christopher A. Maher1,3,6, Chandan Kumar-Sinha1,3,6, Xuhong Cao1,2, Shanker Kalyana-Sundaram1,3, Bo Han1,3, Xiaojun Jing1,3, Lee Sam1,3, Terrence Barrette1,3, Nallasivam Palanisamy1,3 & Arul M. Chinnaiyan1,2,3,4,5
- Michigan Center for Translational Pathology,
- Howard Hughes Medical Institute,
- Department of Pathology,
- Department of Urology,
- Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
- These authors contributed equally to this work.
Correspondence to: Arul M. Chinnaiyan1,2,3,4,5 Correspondence and requests for materials should be addressed to A.M.C. (Email: arul@umich.edu).
Abstract
Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours1, have recently been described in common solid tumours2, 3, 4, 5, 6, 7, 8, 9. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to 're-discover' the BCR–ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2–ERG2, 3 gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.
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Metabolomic profiles delineate potential role for sarcosine in prostate cancer progressionNature Letters to Editor (12 Feb 2009)
Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancerNature Letters to Editor (02 Aug 2007)
TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiationOncogene Scientific Correspondence

