We identify a total of 97 SMGs, including 70 not previously implicated in prostate cancer, such as the ubiquitin ligase CU元 and the transcription factor SPEN. We find that the incidence of significantly mutated genes (SMGs) follows a long-tail distribution, with many genes mutated in less than 3% of cases. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. 22 Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. 21 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 20 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 18 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.1 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 17 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.16 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.15 Centre for Integrated Biology, University of Trento, Trento, Italy.14 Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.13 Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research and Royal Marsden Hospital, London, UK.12 Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College, New York, NY, USA.11 Englander Institute for Precision Medicine, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY, USA.10 Department of Medicine, Division of Medical Oncology, Weill Cornell Medicine, New York, NY, USA.9 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.8 Department of Urology, University of Washington, Seattle, WA, USA.7 Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.6 Department of Medicine, University of Washington, Seattle, WA, USA.5 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.4 Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
3 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
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