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Comprehensive genomic characterization of squamous cell lung cancers
Nature. 2012 Sep;489(7417) :519-525
PMID: WOS:000309167100041    PMCID: PMC3466113   
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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.
Notes
Hammerman, Peter S. Lawrence, Michael S. Voet, Douglas Jing, Rui Cibulskis, Kristian Sivachenko, Andrey Stojanov, Petar McKenna, Aaron Lander, Eric S. Gabriel, Stacey Getz, Gad Sougnez, Carrie Imielinski, Marcin Helman, Elena Hernandez, Bryan Pho, Nam H. Meyerson, Matthew Chu, Andy Chun, Hye-Jung E. Mungall, Andrew J. Pleasance, Erin Robertson, A. Gordon Sipahimalani, Payal Stoll, Dominik Balasundaram, Miruna Birol, Inanc Butterfield, Yaron S. N. Chuah, Eric Coope, Robin J. N. Corbett, Richard Dhalla, Noreen Guin, Ranabir Hirst, Anhe Carrie Hirst, Martin Holt, Robert A. Lee, Darlene Li, Haiyan I. Mayo, Michael Moore, Richard A. Mungall, Karen Nip, Ka Ming Olshen, Adam Schein, Jacqueline E. Slobodan, Jared R. Tam, Angela Thiessen, Nina Varhol, Richard Zeng, Thomas Zhao, Yongjun Jones, Steven J. M. Marra, Marco A. Saksena, Gordon Cherniack, Andrew D. Schumacher, Stephen E. Tabak, Barbara Carter, Scott L. Pho, Nam H. Nguyen, Huy Onofrio, Robert C. Crenshaw, Andrew Ardlie, Kristin Beroukhim, Rameen Winckler, Wendy Hammerman, Peter S. Getz, Gad Meyerson, Matthew Protopopov, Alexei Zhang, Jianhua Hadjipanayis, Angela Lee, Semin Xi, Ruibin Yang, Lixing Ren, Xiaojia Zhang, Hailei Shukla, Sachet Chen, Peng-Chieh Haseley, Psalm Lee, Eunjung Chin, Lynda Park, Peter J. Kucherlapati, Raju Socci, Nicholas D. Liang, Yupu Schultz, Nikolaus Borsu, Laetitia Lash, Alex E. Viale, Agnes Sander, Chris Ladanyi, Marc Auman, J. Todd Hoadley, Katherine A. Wilkerson, Matthew D. Shi, Yan Liquori, Christina Meng, Shaowu Li, Ling Turman, Yidi J. Topal, Michael D. Tan, Donghui Waring, Scot Buda, Elizabeth Walsh, Jesse Jones, Corbin D. Mieczkowski, Piotr A. Singh, Darshan Wu, Junyuan Gulabani, Anisha Dolina, Peter Bodenheimer, Tom Hoyle, Alan P. Simons, Janae V. Soloway, Matthew G. Mose, Lisle E. Jefferys, Stuart R. Balu, Saianand O'Connor, Brian D. Prins, Jan F. Liu, Jinze Chiang, Derek Y. Hayes, D. Neil Perou, Charles M. Cope, Leslie Danilova, Ludmila Weisenberger, Daniel J. Maglinte, Dennis T. Pan, Fei Van den Berg, David J. Triche, Timothy Herman, James G. Baylin, Stephen B. Laird, Peter W. Getz, Gad Noble, Michael Voet, Doug Saksena, Gordon Gehlenborg, Nils DiCara, Daniel Zhang, Jinhua Zhang, Hailei Wu, Chang-Jiun Liu, Spring Yingchun Lawrence, Michael S. Zou, Lihua Sivachenko, Andrey Lin, Pei Stojanov, Petar Jing, Rui Cho, Juok Nazaire, Marc-Danie Robinson, Jim Thorvaldsdottir, Helga Mesirov, Jill Park, Peter J. Chin, Lynda Schultz, Nikolaus Sinha, Rileen Ciriello, Giovanni Cerami, Ethan Gross, Benjamin Jacobsen, Anders Gao, Jianjiong Aksoy, B. Arman Weinhold, Nils Ramirez, Ricardo Taylor, Barry S. Antipin, Yevgeniy Reva, Boris Shen, Ronglai Mo, Qianxing Seshan, Venkatraman Paik, Paul K. Ladanyi, Marc Sander, Chris Akbani, Rehan Zhang, Nianxiang Broom, Bradley M. Casasent, Tod Unruh, Anna Wakefield, Chris Cason, R. Craig Baggerly, Keith A. Weinstein, John N. Haussler, David Benz, Christopher C. Stuart, Joshua M. Zhu, Jingchun Szeto, Christopher Scott, Gary K. Yau, Christina Ng, Sam Goldstein, Ted Waltman, Peter Sokolov, Artem Ellrott, Kyle Collisson, Eric A. Zerbino, Daniel Wilks, Christopher Ma, Singer Craft, Brian Wilkerson, Matthew D. Auman, J. Todd Hoadley, Katherine A. Du, Ying Cabanski, Christopher Walter, Vonn Singh, Darshan Wu, Junyuan Gulabani, Anisha Bodenheimer, Tom Hoyle, Alan P. Simons, Janae V. Soloway, Matthew G. Mose, Lisle E. Jefferys, Stuart R. Balu, Saianand Marron, J. S. Liu, Yufeng Wang, Kai Liu, Jinze Prins, Jan F. Hayes, D. Neil Perou, Charles M. Creighton, Chad J. Zhang, Yiqun Travis, William D. Rekhtman, Natasha Yi, Joanne Aubry, Marie C. Cheney, Richard Dacic, Sanja Flieder, Douglas Funkhouser, William Illei, Peter Myers, Jerome Tsao, Ming-Sound Penny, Robert Mallery, David Shelton, Troy Hatfield, Martha Morris, Scott Yena, Peggy Shelton, Candace Sherman, Mark Paulauskis, Joseph Meyerson, Matthew Baylin, Stephen B. Govindan, Ramaswamy Akbani, Rehan Azodo, Ijeoma Beer, David Bose, Ron Byers, Lauren A. Carbone, David Chang, Li-Wei Chiang, Derek Chu, Andy Chun, Elizabeth Collisson, Eric Cope, Leslie Creighton, Chad J. Danilova, Ludmila Ding, Li Getz, Gad Hammerman, Peter S. Hayes, D. Neil Hernandez, Bryan Herman, James G. Heymach, John Ida, Cristiane Imielinski, Marcin Johnson, Bruce Jurisica, Igor Kaufman, Jacob Kosari, Farhad Kucherlapati, Raju Kwiatkowski, David Ladanyi, Marc Lawrence, Michael S. Maher, Christopher A. Mungall, Andy Ng, Sam Pao, William Peifer, Martin Penny, Robert Robertson, Gordon Rusch, Valerie Sander, Chris Schultz, Nikolaus Shen, Ronglai Siegfried, Jill Sinha, Rileen Sivachenko, Andrey Sougnez, Carrie Stoll, Dominik Stuart, Joshua Thomas, Roman K. Tomaszek, Sandra Tsao, Ming-Sound Travis, William D. Vaske, Charles Weinstein, John N. Weisenberger, Daniel Wheeler, David Wigle, Dennis A. Wilkerson, Matthew D. Wilks, Christopher Yang, Ping Zhang, Jianjua John Jensen, Mark A. Sfeir, Robert Kahn, Ari B. Chu, Anna L. Kothiyal, Prachi Wang, Zhining Snyder, Eric E. Pontius, Joan Pihl, Todd D. Ayala, Brenda Backus, Mark Walton, Jessica Baboud, Julien Berton, Dominique L. Nicholls, Matthew C. Srinivasan, Deepak Raman, Rohini Girshik, Stanley Kigonya, Peter A. Alonso, Shelley Sanbhadti, Rashmi N. Barletta, Sean P. Greene, John M. Pot, David A. Tsao, Ming-Sound Bandarchi-Chamkhaleh, Bizhan Boyd, Jeff Weaver, JoEllen Wigle, Dennis A. Azodo, Ijeoma A. Tomaszek, Sandra C. Aubry, Marie Christine Ida, Christiane M. Yang, Ping Kosari, Farhad Brock, Malcolm V. Rogers, Kristen Rutledge, Marian Brown, Travis Lee, Beverly Shin, James Trusty, Dante Dhir, Rajiv Siegfried, Jill M. Potapova, Olga Fedosenko, Konstantin V. Nemirovich-Danchenko, Elena Rusch, Valerie Zakowski, Maureen Iacocca, Mary V. Brown, Jennifer Rabeno, Brenda Czerwinski, Christine Petrelli, Nicholas Fan, Zhen Todaro, Nicole Eckman, John Myers, Jerome Rathmell, W. Kimryn Thorne, Leigh B. Huang, Mei Boice, Lori Hill, Ashley Penny, Robert Mallery, David Curley, Erin Shelton, Candace Yena, Peggy Morrison, Carl Gaudioso, Carmelo Bartlett, Johnm. S. Kodeeswaran, Sugy Zanke, Brent Sekhon, Harman David, Kerstin Juhl, Hartmut Van Le, Xuan Kohl, Bernard Thorp, Richard Tien, Nguyen Viet Van Bang, Nguyen Sussman, Howard Phu, Bui Duc Hajek, Richard PhiHung, Nguyen Khan, Khurram Z. Muley, Thomas Shaw, Kenna R. Mills Sheth, Margi Yang, Liming Buetow, Ken Davidsen, Tanja Demchok, John A. Eley, Greg Ferguson, Martin Dillon, Laura A. L. Schaefer, Carl Guyer, Mark S. Ozenberger, Bradley A. Palchik, Jacqueline D. Peterson, Jane Sofia, Heidi J. Thomson, Elizabeth Meyerson, Matthew Canc Genome Atlas Res Network Nih [u24 ca126561, u24 ca126551, u24 ca126554, u24 ca126543, u24 ca126546, u24 ca126563, u24 ca126544, u24 ca143845, u24 ca143858, u24 ca144025, u24 ca143882, u24 ca143866, u24 ca143867, u24 ca143848, u24 ca143840, u24 ca143835, u24 ca143799, u24 ca143883, u24 ca143843, u54 hg003067, u54 hg003079, u54 hg003273] This study was supported by NIH grants U24 CA126561, U24 CA126551, U24 CA126554, U24 CA126543, U24 CA126546, U24 CA126563, U24 CA126544, U24 CA143845, U24 CA143858, U24 CA144025, U24 CA143882, U24 CA143866, U24 CA143867, U24 CA143848, U24 CA143840, U24 CA143835, U24 CA143799, U24 CA143883, U24 CA143843, U54 HG003067, U54 HG003079 and U54 HG003273. 46 Nature publishing group London 011lt