Comprehensive genomic characterization of squamous cell lung cancers

Peter S. Hammerman, Doug Voet, Michael S. Lawrence, Douglas Voet, Rui Jing, Kristian Cibulskis, Andrey Sivachenko, Petar Stojanov, Aaron McKenna, Eric S. Lander, Stacey Gabriel, Gad Getz, Marcin Imielinski, Elena Helman, Bryan Hernandez, Nam H. Pho, Matthew Meyerson, Andy Chu, Jung E. Hye-Chun, Andrew J. MungallErin Pleasance, A. Gordon Robertson, Payal Sipahimalani, Dominik Stoll, Miruna Balasundaram, Inanc Birol, Yaron S N Butterfield, Eric Chuah, Robin J N Coope, Richard Corbett, Noreen Dhalla, Ranabir Guin, An He, Carrie Hirst, Martin Hirst, Robert A. Holt, Darlene Lee, Haiyan I. Li, Michael Mayo, Richard A. Moore, Karen Mungall, Ka Ming Nip, Adam Olshen, Jacqueline E. Schein, Jared R. Slobodan, Angela Tam, Nina Thiessen, Richard Varhol, Thomas Zeng, Yongjun Zhao, Steven J M Jones, Marco A. Marra, Gordon Saksena, Andrew D. Cherniack, Stephen E. Schumacher, Barbara Tabak, Scott L. Carter, Huy Nguyen, Robert C. Onofrio, Andrew Crenshaw, Kristin Ardlie, Rameen Beroukhim, Wendy Winckler, Alexei Protopopov, Jianhua Zhang, Angela Hadjipanayis, Semin Lee, Ruibin Xi, Lixing Yang, Xiaojia Ren, Hailei Zhang, Sachet Shukla, Peng Chieh Chen, Psalm Haseley, Eunjung Lee, Lynda Chin, Peter J. Park, Raju Kucherlapati, Nicholas D. Socci, Yupu Liang, Nikolaus Schultz, Laetitia Borsu, Alex E. Lash, Agnes Viale, Chris Sander, Marc Ladanyi, J. Todd Auman, Katherine A. Hoadley, Matthew D. Wilkerson, Yan Shi, Christina Liquori, Shaowu Meng, Ling Li, Yidi J. Turman, Michael D. Topal, Donghui Tan, Scot Waring, Elizabeth Buda, Jesse Walsh, Corbin D. Jones, Piotr A. Mieczkowski, Darshan Singh, Junyuan Wu, Anisha Gulabani, Peter Dolina, Tom Bodenheimer, Alan P. Hoyle, Janae V. Simons, Matthew G. Soloway, Joshua Stuart, Lisle E. Mose, Stuart R. Jefferys, Saianand Balu, Brian D. O'Connor, Derek Chiang, Jinze Liu, Derek Y. Chiang, D. Neil Hayes, Charles M. Perou, Leslie Cope, Daniel Weisenberger, Ludmila Danilova, Daniel J. Weisenberger, Dennis T. Maglinte, Fei Pan, David J. Van Den Berg, Timothy Triche, James G. Herman, Stephen B. Baylin, Peter W. Laird, Michael Noble, Nils Gehlenborg, Daniel DiCara, Jinhua Zhang, Chang Jiun Wu, Spring Yingchun Liu, Lihua Zou, Pei Lin, Juok Cho, Marc Danie Nazaire, Jim Robinson, Helga Thorvaldsdottir, Jill Mesirov, Rileen Sinha, Giovanni Ciriello, Ethan Cerami, Benjamin Gross, Anders Jacobsen, Jianjiong Gao, B. Arman Aksoy, Nils Weinhold, Ricardo Ramirez, Barry S. Taylor, Yevgeniy Antipin, Boris Reva, Qianxing Mo, Venkatraman Seshan, Paul K. Paik, Rehan Akbani, Nianxiang Zhang, Bradley M. Broom, Tod Casasent, Anna Unruh, Chris Wakefield, R. Craig Cason, Keith A. Baggerly, John N. Weinstein, David Haussler, Christopher C. Benz, Joshua M. Stuart, Jingchun Zhu, Christopher Szeto, Gary K. Scott, Christina Yau, Sam Ng, Ted Goldstein, Peter Waltman, Artem Sokolov, Eric Collisson, Kyle Ellrott, Eric A. Collisson, Daniel Zerbino, Singer Ma, Brian Craft, Ying Du, Christopher Cabanski, Vonn Walter, J. S. Marron, Yufeng Liu, Kai Wang, Jan F. Prins, Chad J. Creighton, Yiqun Zhang, William D. Travis, Natasha Rekhtman, Joanne Yi, Marie C. Aubry, Richard Cheney, Sanja Dacic, Douglas Flieder, William Funkhouser, Peter Illei, Jerome Myers, Ming Sound Tsao, Robert Penny, David Mallery, Troy Shelton, Martha Hatfield, Scott Morris, Peggy Yena, Candace Shelton, Mark Sherman, Joseph Paulauskis, Ramaswamy Govindan, Ijeoma Azodo, David Beer, Ron Bose, Lauren A. Byers, David Carbone, Li Wei Chang, Elizabeth Chun, Li Ding, John Heymach, Cristiane Ida, Bruce Johnson, Igor Jurisica, Jacob Kaufman, Farhad Kosari, David Kwiatkowski, Christopher A. Maher, Andy Mungall, William Pao, Martin Peifer, Gordon Robertson, Valerie Rusch, Jill Siegfried, Carrie Sougnez, Roman K. Thomas, Sandra Tomaszek, Charles Vaske, David Wheeler, Dennis A. Wigle, Christopher Wilks, Jianjua John Zhang, Mark A. Jensen, Robert Sfeir, Ari B. Kahn, Anna L. Chu, Prachi Kothiyal, Zhining Wang, Eric E. Snyder, Joan Pontius, Todd D. Pihl, Brenda Ayala, Mark Backus, Jessica Walton, Julien Baboud, Dominique L. Berton, Matthew C. Nicholls, Deepak Srinivasan, Rohini Raman, Stanley Girshik, Peter A. Kigonya, Shelley Alonso, Rashmi N. Sanbhadti, Sean P. Barletta, John M. Greene, David A. Pot, Bizhan Bandarchi-Chamkhaleh, Jeff Boyd, Joellen Weaver, Ijeoma A. Azodo, Sandra C. Tomaszek, Marie Christine Aubry, Christiane M. Ida, Ping Yang, Malcolm V. Brock, Kristen Rogers, Marian Rutledge, Travis Brown, Beverly Lee, James Shin, Dante Trusty, Rajiv Dhir, Jill M. Siegfried, Olga Potapova, Konstantin V. Fedosenko, Elena Nemirovich-Danchenko, Maureen Zakowski, Mary V. Iacocca, Jennifer Brown, Brenda Rabeno, Christine Czerwinski, Nicholas Petrelli, Zhen Fan, Nicole Todaro, John Eckman, W. Kimryn Rathmell, Leigh B. Thorne, Mei Huang, Lori Boice, Ashley Hill, Erin Curley, Carl Morrison, Carmelo Gaudioso, John M S Bartlett, Sugy Kodeeswaran, Brent Zanke, Harman Sekhon, Kerstin David, Hartmut Juhl, Xuan Van Le, Bernard Kohl, Richard Thorp, Nguyen Viet Tien, Nguyen Van Bang, Howard Sussman, Bui Duc Phu, Richard Hajek, Nguyen Phi Hung, Khurram Z. Khan, Thomas Muley, Kenna R. Mills Shaw, Margi Sheth, Liming Yang, Ken Buetow, Tanja Davidsen, John A. Demchok, Greg Eley, Martin Ferguson, Laura A L Dillon, Carl Schaefer, Mark S. Guyer, Bradley A. Ozenberger, Jacqueline D. Palchik, Jane Peterson, Heidi J. Sofia, Elizabeth Thomson, Bruce E. Johnson, Ronglai Shen

Research output: Contribution to journalArticle

2230 Scopus citations

Abstract

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Original languageEnglish (US)
Pages (from-to)519-525
Number of pages7
JournalNature
Volume489
Issue number7417
DOIs
StatePublished - Sep 27 2012

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    Hammerman, P. S., Voet, D., Lawrence, M. S., Voet, D., Jing, R., Cibulskis, K., Sivachenko, A., Stojanov, P., McKenna, A., Lander, E. S., Gabriel, S., Getz, G., Imielinski, M., Helman, E., Hernandez, B., Pho, N. H., Meyerson, M., Chu, A., Hye-Chun, J. E., ... Shen, R. (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489(7417), 519-525. https://doi.org/10.1038/nature11404