Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin
Kristen M. Leraas(University of North Carolina at Chapel Hill), David A. Wheeler, Zhong Chen, Lynda Chin, Todd Pihl, Tai Hsien Ou Yang, Gad Getz, Nikolaus Schultz, Roeland Verhaak, Melisssa Cline, Yuan Yuan, Donna Morton, Dong Yeon Cho, Zhenlin Ju, Nils Gehlenborg, Ludmila Danilova, Travis Zack, Cheng Fan, Yunhu Wan, Yi Han, Elena Helman, Wenbin Liu, Ruibin Xi, Brady Bernard, Núria López-Bigas, Alfred K. Yung, Bradley M. Broom, Grace O. Silva, Jeffrey S. Reid, Ami S. Bhatt, Jiashan Zhang(University of North Carolina at Chapel Hill), Lixing Yang, Carmen Helsel, Jun Li, André Kahles, Todd Wylie, Lovelace J. Luquette, Ranabir Guin, Scott Abbott, Lam Nguyen, Marco A. Marra, Cynthia McAllister, Seth P. Lerner, Payal Sipahimalani, Max D.M. Leiserson, Lauren A. Byers, Giovanni Ciriello, Angela N. Brooks, Eric S. Lander, Rehan Akbani, Stephen J. Chanock, Joonil Jung, Richard A. Gibbs, Kai Ye, Christopher A. Miller, Kosuke Yoshihara, Douglas A. Levine, Julie M. Gastier-Foster, Daniel J. Weisenberger, Yingchun Liu, Carter Van Waes, Katherine A. Hoadley(University of North Carolina at Chapel Hill), D. Neil Hayes, A. Gordon Robertson, Jianjiong Gao, Scott Frazer, Psalm Haseley, Michael T. Ryan, Mark P. Hamilton, Vésteinn Thórsson, Jessica Frick, Barry S. Taylor, Sean E. McGuire, Ricardo Ramírez, John N. Weinstein, Paul T. Spellman, Noreen Dhalla, John W. Wallis, Philip L. Lorenzi, Barbara Tabak, Jennifer Drummond, Joshua M. Stuart, Andy Chu, Mark A. Jensen, Greg Eley, Hailei Zhang, Yiling Lu, James Cleland, Joshua F. McMichael, Robert A. Holt, Samirkumar B. Amin, Wei Zhang, Benjamin P. Berman, HarshaVardhan Doddapaneni, Jun Yao, Dimitris Anastassiou, Alan P. Hoyle, Singer Ma, David Tamborero, Michael Mayo, Sahil Seth, David J. Dooling, Jim M. Eldred, Ilya Shmulevich, Steven E. Schumacher, Craig Pohl, Theo Knijnenburg, Adrian Ally, Ronglai Shen, Andrea Eakin, Ryan Bressler, Miruna Balasundaram, Janae V. Simons, Vincent Magrini, Hoon Kim, Jay Bowen, Kyle Ellrott, Eric Chuah, Chang Wu, Jean C. Zenklusen, Chad J. Creighton, Hui Shen, Steven J.M. Jones, Nianxiang Zhang, Peter W. Laird, Preethi H. Gunaratne, Marc Ladanyi, Heather K. Schmidt, Hye Jung E. Chun, Piotr A. Mieczkowski, S. Onur Sumer, Doug Voet, Andrew Wei Xu, Amie Radenbaugh, Michael Parfenov, J. Todd Auman, Yang Da, David Van Den Berg, Brian Craft, Stephen B. Baylin, Larsson Omberg, Jianhua Zhang, Angeliki Pantazi, Alexei Protopopov, Donghui Tan, Peter J. Park, Jacobsen, Anders, Angela Hadjipanayis, Leng Han, Carrie Sougnez, Junyuan Wu, Catrina C. Fronick, David Haussler, Samuel S. Freeman, William Lee, Huyen Dinh, Evan Paull, Michael D. McLellan, Xingzhi Song, Ari E. Kahn, Darlene Lee, Roy Tarnuzzer, Wei Zhao, Nathan D. Dees, Jacqueline E. Schein, Mary J. Goldman, B. Arman Aksoy, Tom Bodenheimer, Chandra Sekhar Pedamallu, Margi Sheth, Angela Tam, Wei Li, Toshinori Hinoue, Daniel C. Koboldt, Wang, Zhining, Stacey Gabriel, Scott L. Carter, Beifang Niu, Abel González-Pérez, Chia-Chin Wu, Han Liang, Daniel DiCara, Yang Yang, Gordon Saksena, Yaron S.N. Butterfield, Kjong-Van Lehmann, Benjamin J. Raphael, Eunjung Lee, Richard A. Moore, Jaegil Kim, James G. Herman, Martin Hirst, Yasin Şenbabaoğlu, Lisa Wise, Cyriac Kandoth, Mary E. Edgerton, Stephen C. Benz, Liming Yang, Lisle E. Mose, Matthew D. Wilkerson, Chris Sander, Tanja M. Davidsen, Christopher C. Benz, Gideon Dresdner, Eric A. Collisson, Umadevi Veluvolu, Richard Varhol, Jiabin Tang, Rong Yao, Raju Kucherlapati, Rileen Sinha, Boris Reva, Adam A. Margolin, Kristian Cibulskis, Harshad S. Mahadeshwar, Erik Zmuda, David W. Kane, Christie Kovar, Xiaojia Ren, Myra M. George, Nilsa C. Ramirez, Shelley M. Herbrich, Teresa Swatloski, Zeng, Dong, Petar Stojanov, Timothy J. Triche, Vladislav Uzunangelov, Yuexin Liu, Jason R. Dobson, Siyuan Zheng, Li Ding, Nils Weinhold, Moiz Bootwalla, Sheila M. Reynolds, Christina Yau, Stuart R. Jeffreys, Lucinda Fulton, Semin Lee, Donna M. Muzny, Laura J. van’t Veer, Jonathan G. Seidman, Kyle Chang, Lisa Iype, Peter Waltman, Tod D. Casasent, Hsin Ta Wu, Elizabeth Buda, David I. Heiman, Chip Stewart, Zheng Xia, Kim D. Delehaunty, Kenneth Aldape, Heidi J. Sofia, Timothy J. Ley, Andrew D. Cherniack, Gordon B. Mills, Andrew J. Mungall, Suhn K. Rhie, Qunyuan Zhang, Richard Kreisberg, Michelle D. O’Laughlin, Ling Lin, Ina Felau, Teresa M. Przytycka, Margaret Morgan, Rachel Abbott, Krishna Kanchi, Michael C. Wendl, Aaron D. Black, David E. Larson, Benjamin Groß, Juok Cho, Joelle Kalicki-Veizer, Christopher A. Bristow, Yichao Sun, Suzanne S. Fei, Divya Kalra, Shaowu Meng, Akinyemi I. Ojesina, Sam Ng, Sofie R. Salama, John A. Demchok, Keith Baggerly, Deepti Dodda, Mathew G. Soloway, Waring, Scot, Robert S. Fulton, Samantha Sharpe, Hollie A. Harper, Michael S. Noble, Brad Ozenberger, Scott M. Smith, Haiyan I. Li, Nina Thiessen, Lihua Zou, Joel S. Parker, Houtan Noushmehr, Charles M. Perou(University of North Carolina at Chapel Hill), David Pot, Charles Lu, James Melott, Andrew L. Wong, Xi Liu, Carlin, Daniel, Louis M. Staudt, Lora Lewis, Robert Burton, Tara M. Lichtenberg, Denise M. Wolf, Jake Lin, Kalle Leinonen, Jing Zhu, Stanley R. Hamilton, Pei Lin, Martin L. Miller, Jeffrey Roach, Fabio Vandin, Lawrence A. Donehower, Gunnar Rätsch, Richard K. Wilson, Carrie Hirst, Michael Miller, İnanç Birol, Artem Sokolov, Corbin D. Jones, Wenyi Wang, Elaine R. Mardis, Michael S. Lawrence, Caleb Davis, Saianand Balu, Hector Rovira, Min Wang, Charles Vaske, Yan Shi, Xiaoping Su, Netty Santoso, Jason Walker, Roger Kramer, Matthew Meyerson
Cited by 0Open Access
Abstract
Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.
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