Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets Journal Article


Authors: Wedge, D. C.; Gundem, G.; Mitchell, T.; Woodcock, D. J.; Martincorena, I.; Ghori, M.; Zamora, J.; Butler, A.; Whitaker, H.; Kote-Jarai, Z.; Alexandrov, L. B.; Van Loo, P.; Massie, C. E.; Dentro, S.; Warren, A. Y.; Verrill, C.; Berney, D. M.; Dennis, N.; Merson, S.; Hawkins, S.; Howat, W.; Lu, Y. J.; Lambert, A.; Kay, J.; Kremeyer, B.; Karaszi, K.; Luxton, H.; Camacho, N.; Marsden, L.; Edwards, S.; Matthews, L.; Bo, V.; Leongamornlert, D.; McLaren, S.; Ng, A.; Yu, Y.; Zhang, H.; Dadaev, T.; Thomas, S.; Easton, D. F.; Ahmed, M.; Bancroft, E.; Fisher, C.; Livni, N.; Nicol, D.; Tavaré, S.; Gill, P.; Greenman, C.; Khoo, V.; Van As, N.; Kumar, P.; Ogden, C.; Cahill, D.; Thompson, A.; Mayer, E.; Rowe, E.; Dudderidge, T.; Gnanapragasam, V.; Shah, N. C.; Raine, K.; Jones, D.; Menzies, A.; Stebbings, L.; Teague, J.; Hazell, S.; Corbishley, C.; CAMCAP Study Group; de Bono, J.; Attard, G.; Isaacs, W.; Visakorpi, T.; Fraser, M.; Boutros, P. C.; Bristow, R. G.; Workman, P.; Sander, C.; TCGA Consortium; Hamdy, F. C.; Futreal, A.; McDermott, U.; Al-Lazikani, B.; Lynch, A. G.; Bova, G. S.; Foster, C. S.; Brewer, D. S.; Neal, D. E.; Cooper, C. S.; Eeles, R. A.
Contributors: Armenia, J.; Arora, A.; Chang, M.; Chen, Y.; Gao, J.; Gopalan, A.; Kahles, A.; Lehmann, K. V.; Rätsch, G.; Reuter, V.; Schultz, N.; Shen, R.; Taylor, B. S.; Wang, Q.; Weinhold, N.; Zhong, Y.
Article Title: Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets
Abstract: Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials. © 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: 682
End Page: 692
Language: English
DOI: 10.1038/s41588-018-0086-z
PROVIDER: scopus
PUBMED: 29662167
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Yu Chen
    67 Chen
  2. Ronglai Shen
    127 Shen
  3. Anuradha Gopalan
    273 Gopalan
  4. Victor Reuter
    900 Reuter
  5. Jianjiong Gao
    62 Gao
  6. Barry Stephen Taylor
    138 Taylor
  7. Nikolaus D Schultz
    196 Schultz
  8. Gunnar Ratsch
    45 Ratsch
  9. Andre Kahles
    15 Kahles
  10. Yi Zhong
    13 Zhong
  11. Arshi Arora
    19 Arora
  12. Matthew   Chang
    21 Chang
  13. Qingguo   Wang
    5 Wang
  14. Joshua   Armenia
    22 Armenia
  15. Gunes Gundem
    9 Gundem