The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Christopher J Ricketts; Aguirre A De Cubas; Huihui Fan; Christof C Smith; Martin Lang; Ed Reznik; Reanne Bowlby; Ewan A Gibb; Rehan Akbani; Rameen Beroukhim; Donald P Bottaro; Toni K Choueiri; Richard A Gibbs; Andrew K Godwin; Scott Haake; A Ari Hakimi; Elizabeth P Henske; James J Hsieh; Thai H Ho; Rupa S Kanchi; Bhavani Krishnan; David J Kwiatkowski; Wenbin Liu; Maria J Merino; Gordon B Mills; Jerome Myers; Michael L Nickerson; Victor E Reuter; Laura S Schmidt; C Simon Shelley; Hui Shen; Brian Shuch; Sabina Signoretti; Ramaprasad Srinivasan; Pheroze Tamboli; George Thomas; Benjamin G Vincent; Cathy D Vocke; David A Wheeler; Lixing Yang; William Y Kim; A Gordon Robertson; Cancer Genome Atlas Research Network; Paul T Spellman; W Kimryn Rathmell; W Marston Linehan

doi:10.1016/j.celrep.2018.03.075

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Cell Rep. 2018 Apr 3;23(1):313-326.e5. doi: 10.1016/j.celrep.2018.03.075.

Authors

Christopher J Ricketts¹, Aguirre A De Cubas², Huihui Fan³, Christof C Smith⁴, Martin Lang¹, Ed Reznik⁵, Reanne Bowlby⁶, Ewan A Gibb⁶, Rehan Akbani⁷, Rameen Beroukhim⁸, Donald P Bottaro¹, Toni K Choueiri⁹, Richard A Gibbs¹⁰, Andrew K Godwin¹¹, Scott Haake², A Ari Hakimi⁵, Elizabeth P Henske¹², James J Hsieh¹³, Thai H Ho¹⁴, Rupa S Kanchi⁷, Bhavani Krishnan⁴, David J Kwiatkowski¹², Wenbin Liu⁷, Maria J Merino¹⁵, Gordon B Mills⁷, Jerome Myers¹⁶, Michael L Nickerson¹⁷, Victor E Reuter⁵, Laura S Schmidt¹⁸, C Simon Shelley¹⁹, Hui Shen³, Brian Shuch²⁰, Sabina Signoretti⁹, Ramaprasad Srinivasan¹, Pheroze Tamboli⁷, George Thomas²¹, Benjamin G Vincent⁴, Cathy D Vocke¹, David A Wheeler¹⁰, Lixing Yang²², William Y Kim⁴, A Gordon Robertson⁶; Cancer Genome Atlas Research Network; Paul T Spellman²¹, W Kimryn Rathmell², W Marston Linehan²³

Collaborators

Cancer Genome Atlas Research Network:
Samantha J Caesar-Johnson, John A Demchok, Ina Felau, Melpomeni Kasapi, Martin L Ferguson, Carolyn M Hutter, Heidi J Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C Zenklusen, Jiashan Julia Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I Heiman, Jaegil Kim, Michael S Lawrence, Pei Lin, Sam Meier, Michael S Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M Broom, Apurva M Hegde, Zhenlin Ju, Rupa S Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E Gross, Zachary J Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G Nissan, Angelica Ochoa, Sarah M Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S Onur Sumer, Yichao Sun, Barry S Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M Stuart, Christopher K Wong, Christina Yau, D Neil Hayes, Joel S Parker, Matthew D Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J M Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A Marra, Michael Mayo, Richard A Moore, Andrew J Mungall, Karen Mungall, A Gordon Robertson, Sara Sadeghi, Jacqueline E Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C Berger, Rameen Beroukhim, Andrew D Cherniack, Carrie Cibulskis, Stacey B Gabriel, Galen F Gao, Gavin Ha, Matthew Meyerson, Steven E Schumacher, Juliann Shih, Melanie H Kucherlapati, Raju S Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S Bootwalla, Phillip H Lai, Dennis T Maglinte, David J Van Den Berg, Daniel J Weisenberger, J Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A Hoadley, Alan P Hoyle, Stuart R Jefferys, Corbin D Jones, Shaowu Meng, Piotr A Mieczkowski, Lisle E Mose, Amy H Perou, Charles M Perou, Jeffrey Roach, Yan Shi, Janae V Simons, Tara Skelly, Matthew G Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A Donehower, Jennifer Drummond, Richard A Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L Appelbaum, Matthew Bailey, Matthew G Cordes, Li Ding, Catrina C Fronick, Lucinda A Fulton, Robert S Fulton, Cyriac Kandoth, Elaine R Mardis, Michael D McLellan, Christopher A Miller, Heather K Schmidt, Richard K Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M Gastier-Foster, Mark Gerken, Kristen M Leraas, Tara M Lichtenberg, Nilsa C Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L Carvalho, Ana C de Carvalho, José H Fregnani, Adhemar Longatto-Filho, Rui M Reis, Cristovam Scapulatempo-Neto, Henrique C S Silveira, Daniel O Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L Anderson, Patricia D Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P Raut, Andrei Malykh, Jill S Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y Karlan, Curt H Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M Shin, Gabriel Sica, Erwin G Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E van Kessel, Ellen C Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R Dottino, John A Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H Bryce, Erik Castle, Vishal Chandan, John Cheville, John A Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O'Brien, Brian Patrick O'Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Onathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W Marston Linehan, Adam R Metwalli, Karel Pacak, Peter A Pinto, Mark Schiffman, Laura S Schmidt, Cathy D Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M Rassl, Robert C Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A Borgia, Michael J Liptay, Mark Pool, Christopher W Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M Cebulla, Amy Davis, Rebecca Duell, J Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E Grizzle, Katherine C Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R Carroll, June M Chan, Philip Disaia, Pat Glenn, Robin K Kelley, Charles N Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K Godwin, Rashna Madan, Howard G Rosenthal, Clement Adebamowo, Sally N Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti Jr, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M Fong, Ian Yang, Robert Korst, W Kimryn Rathmell, J Leigh Fantacone-Campbell, Jeffrey A Hooke, Albert J Kovatich, Craig D Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A Rubin, Jung Il Lee, Natália D Aredes, Armaz Mariamidze

Affiliations

¹ Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA.
² Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
³ Van Andel Research Institute, Grand Rapids, MI 49503, USA.
⁴ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁶ Canada's Michael Smith Genome Sciences Centre, Vancouver, BC V5Z 4S6, Canada.
⁷ The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁸ The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
⁹ Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹⁰ Baylor College of Medicine, Houston, TX 77030, USA.
¹¹ University of Kansas Medical Center, Kansas City, KS 66206, USA.
¹² Brigham and Women's Hospital, Boston, MA 02115, USA.
¹³ Washington University School of Medicine, St. Louis, MO 63110, USA.
¹⁴ Mayo Clinic Arizona, Phoenix, AZ 85054, USA.
¹⁵ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁶ Centura Health, Centennial, CO 80112, USA.
¹⁷ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁸ Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA; Basic Science Program, Leidos Biomedical Research, Inc. Frederick National Laboratory of Cancer Research, Frederick, MD 21702, USA.
¹⁹ Leukemia Therapeutics LLC., Hull, MA 02045, USA.
²⁰ Yale University, New Haven, CT 06520, USA.
²¹ Oregon Health & Science University, Portland, OR 97239, USA.
²² Harvard Medical School, Boston, MA 02115, USA.
²³ Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA. Electronic address: wml@nih.gov.

Abstract

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

Keywords: CDKN2A; DNA hypermethylation; PanCanAtlas; TCGA; chromatin remodeling; chromophobe renal cell carcinoma; clear cell renal cell carcinoma; immune signature; papillary renal cell carcinoma.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Biomarkers, Tumor / genetics*
Biomarkers, Tumor / immunology
Biomarkers, Tumor / metabolism
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / metabolism
Carcinoma, Renal Cell / pathology
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
DNA-Binding Proteins
Genome, Human*
Humans
Kidney Neoplasms / genetics*
Kidney Neoplasms / metabolism
Kidney Neoplasms / pathology
Metabolic Networks and Pathways
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Phenotype
Survival Analysis
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Suppressor Proteins / genetics
Ubiquitin Thiolesterase / genetics

Substances

BAP1 protein, human
Biomarkers, Tumor
CDKN2A protein, human
Cyclin-Dependent Kinase Inhibitor p16
DNA-Binding Proteins
Nuclear Proteins
PBRM1 protein, human
Transcription Factors
Tumor Suppressor Proteins
PTEN Phosphohydrolase
PTEN protein, human
Ubiquitin Thiolesterase

Abstract

Publication types

MeSH terms

Substances

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