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

Autor: Luke Marsden, Colin Cooper, Jorge Zamora, Barbara Kremeyer, Jonathan Kay, Steven Hazell, Mahbubl Ahmed, Tim Dudderidge, Edward Rowe, Hongwei Zhang, William Howat, Freddie C. Hamdy, Tapio Visakorpi, Paul C. Boutros, Gunes Gundem, Bissan Al-Lazikani, S. Edwards, David C. Wedge, Inigo Martincorena, Charles E. Massie, Douglas F. Easton, Gerhardt Attard, Nicholas van As, Anne Y. Warren, Dan J. Woodcock, Naomi Livni, Johann S. de Bono, Nening Dennis, Adam Lambert, Clare Verrill, Alan Thompson, Niedzica Camacho, Daniel Leongamornlert, William B. Isaacs, Christopher S. Foster, Hayley C. Whitaker, Pardeep Kumar, Daniel Brewer, Christopher Greenman, Declan Cahill, Simon Tavaré, Yong-Jie Lu, Stuart McLaren, Ultan McDermott, David T. Jones, Sue Merson, Rosalind A. Eeles, Vincent Khoo, Steve Hawkins, Daniel M. Berney, Cyril Fisher, Hayley J. Luxton, Lucy Matthews, Ludmil B. Alexandrov, G. Steven Bova, Adam Butler, David Nicol, Andy G. Lynch, Michael Fraser, Tokhir Dadaev, Keiran Raine, Mohammed J. R. Ghori, Katalin Karaszi, Jon W. Teague, Chris Sander, Robert G. Bristow, Peter Van Loo, Nimish Shah, Chris Ogden, Paul Workman, Andrew Menzies, Lucy Stebbings, Stefan C. Dentro, Cathy Corbishley, Thomas J. Mitchell, Zsofia Kote-Jarai, Pelvender Gill, Andrew Futreal, Elizabeth Bancroft, David E. Neal, Sarah Thomas, Anthony C. H. Ng, Erik Mayer, Yongwei Yu, Vincent Gnanapragasam, Valeria Bo
Přispěvatelé: University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Aging
medicine.disease_cause
Medical and Health Sciences
Metastasis
Prostate cancer
Prostate
80 and over
2.1 Biological and endogenous factors
Aetiology
R2C
Cancer
Aged
80 and over
Mutation
Prostate Cancer
~DC~
High-Throughput Nucleotide Sequencing
Middle Aged
Biological Sciences
BRCA2 Protein
medicine.anatomical_structure
5.1 Pharmaceuticals
Disease Progression
Development of treatments and therapeutic interventions
BDC
Biotechnology
Adult
Hepatocyte Nuclear Factor 3-alpha
Urologic Diseases
RM
Copy number analysis
and over
Biology
Article
RC0254
03 medical and health sciences
SDG 3 - Good Health and Well-being
medicine
Genetics
Humans
Aged
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Human Genome
Prostatic Neoplasms
DAS
Oncogenes
medicine.disease
T Technology
RM Therapeutics. Pharmacology
Clinical trial
030104 developmental biology
TCGA Consortium
CAMCAP Study Group
Cancer research
Cancer biomarkers
Developmental Biology
Zdroj: Nature genetics, vol 50, iss 5
ISSN: 1546-1718
1061-4036
Popis: 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. Postprint
Databáze: OpenAIRE
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