The long tail of oncogenic drivers in prostate cancer Journal Article


Authors: Armenia, J.; Wankowicz, S. A. M.; Liu, D.; Gao, J.; Kundra, R.; Reznik, E.; Chatila, W. K.; Chakravarty, D.; Han, G. C.; Coleman, I.; Montgomery, B.; Pritchard, C.; Morrissey, C.; Barbieri, C. E.; Beltran, H.; Sboner, A.; Zafeiriou, Z.; Miranda, S.; Bielski, C. M.; Penson, A. V.; Tolonen, C.; Huang, F. W.; Robinson, D.; Wu, Y. M.; Lonigro, R.; Garraway, L. A.; Demichelis, F.; Kantoff, P. W.; Taplin, M. E.; Abida, W.; Taylor, B. S.; Scher, H. I.; Nelson, P. S.; de Bono, J. S.; Rubin, M. A.; Sawyers, C. L.; Chinnaiyan, A. M.; PCF/SU2C International Prostate Cancer Dream Team; Schultz, N.; Van Allen, E. M.
Contributors: Vinson, J.; Chen, Y.; Rathkopf, D. E.; Morris, M. J.; Solomon, S. B.; Durack, J. C.; Reuter, V. E.; Gopalan, A.
Article Title: The long tail of oncogenic drivers in prostate cancer
Abstract: Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. 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. 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 a total of 97 SMGs, including 70 not previously implicated in prostate cancer, such as the ubiquitin ligase CUL3 and the transcription factor SPEN. Finally, comparing primary and metastatic prostate cancer identifies a set of genomic markers that may inform risk stratification. © 2018 The Author(s).
Journal Title: Nature Genetics
Volume: 50
Issue: 5
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2018-05-01
Start Page: 645
End Page: 651
Language: English
DOI: 10.1038/s41588-018-0078-z
PROVIDER: scopus
PUBMED: 29610475
PMCID: PMC6107367
DOI/URL:
Notes: Article -- Correction issued, see DOI 10.1038/s41588-019-0451-6 -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Charles L Sawyers
    226 Sawyers
  2. Jacob Vinson
    8 Vinson
  3. Michael Morris
    578 Morris
  4. Yu Chen
    133 Chen
  5. Anuradha Gopalan
    417 Gopalan
  6. Stephen Solomon
    424 Solomon
  7. Dana Elizabeth Rathkopf
    273 Rathkopf
  8. Victor Reuter
    1228 Reuter
  9. Howard Scher
    1130 Scher
  10. Jianjiong Gao
    132 Gao
  11. Wassim Abida
    157 Abida
  12. Barry Stephen Taylor
    238 Taylor
  13. Nikolaus D Schultz
    488 Schultz
  14. Jeremy Charles Durack
    116 Durack
  15. Eduard Reznik
    103 Reznik
  16. Alexander Vincent Penson
    54 Penson
  17. Philip Wayne Kantoff
    198 Kantoff
  18. Joshua   Armenia
    56 Armenia
  19. Ritika   Kundra
    89 Kundra
  20. Craig Bielski
    23 Bielski
  21. Walid Khaled Chatila
    102 Chatila