Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.
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Authors
Wedge, DC
Gundem, G
Mitchell, T
Woodcock, DJ
Martincorena, I
Ghori, M
Zamora, J
Butler, A
Whitaker, H
Kote-Jarai, Z
Alexandrov, LB
Van Loo, P
Massie, CE
Dentro, S
Warren, AY
Verrill, C
Berney, DM
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, DF
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, NC
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, PC
Bristow, RG
Workman, P
Sander, C
TCGA Consortium,
Hamdy, FC
Futreal, A
McDermott, U
Al-Lazikani, B
Lynch, AG
Bova, GS
Foster, CS
Brewer, DS
Neal, DE
Cooper, CS
Eeles, RA
Gundem, G
Mitchell, T
Woodcock, DJ
Martincorena, I
Ghori, M
Zamora, J
Butler, A
Whitaker, H
Kote-Jarai, Z
Alexandrov, LB
Van Loo, P
Massie, CE
Dentro, S
Warren, AY
Verrill, C
Berney, DM
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, DF
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, NC
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, PC
Bristow, RG
Workman, P
Sander, C
TCGA Consortium,
Hamdy, FC
Futreal, A
McDermott, U
Al-Lazikani, B
Lynch, AG
Bova, GS
Foster, CS
Brewer, DS
Neal, DE
Cooper, CS
Eeles, RA
Document Type
Journal Article
Date
2018-05-01
Date Accepted
2018-02-22
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.
Citation
Nature genetics, 2018, 50 (5), pp. 682 - 692
DOI
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
eISSN
Research Team
Computational Biology and Chemogenomics
Prostate Cancer Targeted Therapy Group
Oncogenetics
Stereotactic and Precision Body Radiotherapy
Prostate Cancer Targeted Therapy Group
Oncogenetics
Stereotactic and Precision Body Radiotherapy