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

Wedge, David C., Gundem, Gunes, Mitchell, Thomas, Woodcock, Dan J., Martincorena, Inigo, Ghori, Mohammed, Zamora, Jorge, Butler, Adam, Whitaker, Hayley, Kote-Jarai, Zsofia, Alexandrov, Ludmil B., Van Loo, Peter, Massie, Charlie E., Dentro, Stefan, Warren, Anne Y., Verrill, Clare, Berney, Dan M., Dennis, Nening, Merson, Sue, Hawkins, Steve, Howat, William, Lu, Yong-Jie, Lambert, Adam, Kay, Jonathan, Kremeyer, Barbara, Karaszi, Katalin, Luxton, Hayley, Camacho, Niedzica, Marsden, Luke, Edwards, Sandra, Matthews, Lucy, Bo, Valeria, Leongamornlert, Daniel, McLaren, Stuart, Ng, Anthony, Yu, Yongwei, Zhang, Hongwei, Dadaev, Tokhir, Thomas, Sarah, Easton, Douglas F., Ahmed, Mahbubl, Bancroft, Elizabeth, Fisher, Cyril, Livni, Naomi, Nicol, David, Tavaré, Simon, Gill, Pelvender, Greenman, Christopher, Khoo, Vincent, Van As, Nicholas, Kumar, Pardeep, Ogden, Christopher, Cahill, Declan, Thompson, Alan, Mayer, Erik, Rowe, Edward, Dudderidge, Tim, Gnanapragasam, Vincent, Shah, Nimish C., Raine, Keiran, Jones, David, Menzies, Andrew, Stebbings, Lucy, Teague, Jon, Hazell, Steven, Corbishley, Cathy, de Bono, Johann, Attard, Gerhardt, Isaacs, William, Visakorpi, Tapio, Fraser, Michael, Boutros, Paul C., Bristow, Robert G., Workman, Paul, Sander, Chris, Hamdy, Freddie C., Futreal, Andrew, McDermott, Ultan, Al-Lazikani, Bissan, Lynch, Andrew G., Bova, G. Steven, Foster, Christopher S., Brewer, Daniel S., Neal, David E., Cooper, Colin S. and Eeles, Rosalind A. (2018) Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets. Nature Genetics, 50. 682–692. ISSN 1061-4036

[img]
Preview
PDF (Accepted manuscript) - Submitted Version
Download (2MB) | Preview

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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Computing Sciences

University of East Anglia > Faculty of Science > Research Groups > Computational Biology (subgroups are shown below) > Analysis and models of genomic variation
Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: Pure Connector
Date Deposited: 16 Jan 2018 10:30
Last Modified: 28 Aug 2020 23:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/65943
DOI: 10.1038/s41588-018-0086-z

Actions (login required)

View Item View Item