Authors
Cancer Genome Atlas Research Network Analysis working group: Baylor College of Medicine Creighton Chad J. 1 2 Morgan Margaret 1 Gunaratne Preethi H. 1 3 Wheeler David A. 1 Gibbs Richard A. 1, BC Cancer Agency Gordon Robertson A. 4 Chu Andy 4, Broad Institute Beroukhim Rameen 5 6 Cibulskis Kristian 6, Brigham & Women’s Hospital Signoretti Sabina 7 54 59, Brown University Vandin Hsin-Ta Wu Fabio 8 8 Raphael Benjamin J. 8, University of Texas MD Anderson Cancer Center Verhaak Roel GW 9 Tamboli Pheroze 10 Torres-Garcia Wandaliz 9 Akbani Rehan 9 Weinstein John N. 9, Memorial Sloan-Kettering Cancer Center Reuter Victor 11 Hsieh James J. 12 Rose Brannon A. 11 Ari Hakimi A. 12 Jacobsen Anders 13 Ciriello Giovanni 13 Reva Boris 13, National Cancer Institute Ricketts Christopher J. 14 Marston Linehan W. agibbs@ bcm. edu 14 c, University of California Santa Cruz Stuart Joshua M. 15, University of North Carolina, Chapel Hill Kimryn Rathmell W. 16, University of Southern California Shen Hui 17 Laird Peter W. 17, Broad Institute Getz Gad 6 57 Cibulskis Kristian 6 Lawrence Michael S. 6 Sougnez Carrie 6 Carter Scott L. 6 Sivachenko Andrey 6 Lichtenstein Lee 6 Stewart Chip 6 Voet Doug 6 Fisher Sheila 6 Gabriel Stacey B. 6 Lander Eric 6, Harvard Medical School Kucherlapati Raju 24 25 Park Peter 25 26 27, Genome data analysis: Baylor College of Medicine Creighton Chad J. 1 2 Wheeler David A. 1, Brown University Vandin Fabio 8 Wu Hsin-Ta 8 Raphael Benjamin J. 8, Buck Institute for Research on Aging Benz Christopher 55 Yau Christina 55, Institute for Systems Biology Reynolds Sheila M. 29 Shmulevich Ilya 29, Oregon Health & Science University Fei Suzanne S. 33 Stout Andrew 33 Spellman Paul T. 33, Stanford University Rubin Daniel L. 34 Liu Tiffany T. 34, University of California Santa Cruz Stuart Joshua M. 15 Ng Sam 15 Paull Evan O. 15 Carlin Daniel 15 Goldstein Theodore 15 Waltman Peter 15 Ellrott Kyle 15 Zhu Jing 15 Haussler David 15 35, University of Houston Gunaratne Preethi H. 1 3 Xiao Weimin 3, Biospecimen core resource: International Genomics Consortium Shelton Candace 36 Gardner Johanna 36 Penny Robert 36 Sherman Mark 36 Mallery David 36 Morris Scott 36 Paulauskis Joseph 36 Burnett Ken 36 Shelton Troy 36, Tissue source sites: Brigham & Women’s Hospital Signoretti Sabina 7 54 59, Dana-Farber Cancer Institute Kaelin William G. 54 60 Choueiri Toni 54, Georgetown University Atkins Michael B. 37, International Genomics Consortium Penny Robert 36 Burnett Ken 36 Mallery David 36 Curley Erin 36, Memorial Sloan-Kettering Cancer Center Tickoo Satish 11 Reuter Victor 11, University of North Carolina at Chapel Hill Kimryn Rathmell W. 16 Thorne Leigh 16 Boice Lori 16 Huang Mei 16 Fisher Jennifer C. 16, National Cancer Institute Marston Linehan W. agibbs@ bcm. edu 14 b Vocke Cathy D. 14 Peterson James 14 Worrell Robert 14 Merino Maria J. 14 Schmidt Laura S. 14 38, University of Texas MD Anderson Cancer Center Tamboli Pheroze 10 Czerniak Bogdan A. 10 Aldape Kenneth D. 10 Wood Christopher G. 39, Fox Chase Cancer Center Boyd Jeff 40 Weaver JoEllen 40, Helen F Graham Cancer Center at Christiana Care Iacocca Mary V. 41 Petrelli Nicholas 41 Witkin Gary 41 Brown Jennifer 41 Czerwinski Christine 41 Huelsenbeck-Dill Lori 41 Rabeno Brenda 41, Penrose-St. Francis Health Services Myers Jerome 42 Morrison Carl 42 Bergsten Julie 42 Eckman John 42 Harr Jodi 42 Smith Christine 42 Tucker Kelinda 42 Anne Zach Leigh 42, Roswell Park Cancer Institute Bshara Wiam 43 Gaudioso Carmelo 43 Morrison Carl 43, University of Pittsburgh Dhir Rajiv 44 Maranchie Jodi 44 Nelson Joel 44 Parwani Anil 44, Cureline Potapova Olga 45, St. Petersburg City Clinical Oncology Dispensary Fedosenko Konstantin 46, Mayo Clinic Cheville John C. 58 Houston Thompson R. 58, Disease working group: Brigham & Women’s Hospital Signoretti Sabina 7 54 59, Dana-Farber Cancer Institute Kaelin William G. 54 60, Georgetown University Atkins Michael B. 37, Memorial Sloan-Kettering Cancer Center Tickoo Satish 11 Reuter Victor 11, National Cancer Institute Marston Linehan W. agibbs@ bcm. edu 14 b Vocke Cathy D. 14 Peterson James 14 Merino Maria J. 14 Schmidt Laura S. 14 38, University of Texas MD Anderson Cancer Center Tamboli Pheroze 10, Weill Cornell Medical College Mosquera Juan M. 47 Rubin Mark A. 47, Massachusetts General Hospital Blute Michael L. 48, University of North Carolina, Chapel Hill Kimryn Rathmell W. 16, Project team: National Cancer Institute Sheth Margi 50 Demchok John A. 50 Davidsen Tanja 50 Wang Zhining 50 Yang Liming 50 Tarnuzzer Roy W. 50 Zhang Jiashan 50 Eley Greg 51 Ferguson Martin L. 52 Mills Shaw Kenna R. 50, National Human Genome Research Institute Guyer Mark S. 53 Ozenberger Bradley A. 53 Sofia. Heidi J. 53
Publication date
2013/7/4
Journal
Nature
Volume
499
Issue
7456
Pages
43-49
Publisher
Nature Publishing Group UK
Description
Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of …
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