Comprehensive genomic characterization of squamous cell lung cancers.
The Cancer Genome Atlas Research Network (Participants are arranged by area of contribution and then by institution.); Genome sequencing centres: Broad Institute; Hammerman, Peter S. 2,3; Lawrence, Michael S. 2; Voet, Douglas 2; Jing, Rui 2; Cibulskis, Kristian 2; Sivachenko, Andrey 2; Stojanov, Petar 2; McKenna, Aaron 2; Lander, Eric S. 2,4,5; Gabriel, Stacey 6; Getz, Gad 2,6; Sougnez, Carrie 5,6; Imielinski, Marcin 2,7; Helman, Elena 2; Hernandez, Bryan 2; Pho, Nam H. 2; Meyerson, Matthew 2,3,7; Genome characterization centres: BC Cancer Agency; Chu, Andy 8; Chun, Hye-Jung E. 8; Mungall, Andrew J. 8; Pleasance, Erin 8; Gordon Robertson, A. 8; Sipahimalani, Payal 8; Stoll, Dominik 8; Balasundaram, Miruna 8; Birol, Inanc 8; Butterfield, Yaron S. N. 8; Chuah, Eric 8; Coope, Robin J. N. 8; Corbett, Richard 8; Dhalla, Noreen 8; Guin, Ranabir 8; He, An 8; Hirst, Carrie 8; Hirst, Martin 8; Holt, Robert A. 8; Lee, Darlene 8; Li, Haiyan I. 8; Mayo, Michael 8; Moore, Richard A. 8; Mungall, Karen 8; Ming Nip, Ka 8; Olshen, Adam 9; Schein, Jacqueline E. 8; Slobodan, Jared R. 8; Tam, Angela 8; Thiessen, Nina 8; Varhol, Richard 8; Zeng, Thomas 8; Zhao, Yongjun 8; Jones, Steven J. M. 8; Marra, Marco A. 8; Broad Institute; Saksena, Gordon 2; Cherniack, Andrew D. 2; Schumacher, Stephen E. 2,3; Tabak, Barbara 2,3; Carter, Scott L. 2; Nguyen, Huy 2; Onofrio, Robert C. 6; Crenshaw, Andrew 2; Ardlie, Kristin 6; Beroukhim, Rameen 2,3; Winckler, Wendy 2,6; Brigham & Women's HospitalHarvard Medical School /; Protopopov, Alexei 10,11; Zhang, Jianhua 10,11; Hadjipanayis, Angela 12,13; Lee, Semin 14; Xi, Ruibin 14; Yang, Lixing 14; Ren, Xiaojia 10,12,13; Zhang, Hailei 2,10; Shukla, Sachet 2,10; Chen, Peng-Chieh 12,13; Haseley, Psalm 13,14; Lee, Eunjung 13,14; Chin, Lynda 2,3,10,11,15; Park, Peter J. 13,14,16; Kucherlapati, Raju 12,13; Memorial Sloan-Kettering Cancer Center (TCGA pilot phase only); Socci, Nicholas D. 17; Liang, Yupu 17; Schultz, Nikolaus 17; Borsu, Laetitia 17; Lash, Alex E. 17; Viale, Agnes 17; Sander, Chris 17; Ladanyi, Marc 18,19; University of North Carolina at Chapel Hill; Todd Auman, J. 20,21; Hoadley, Katherine A. 22,23,24; Wilkerson, Matthew D. 24; Shi, Yan 24; Liquori, Christina 24; Meng, Shaowu 24; Li, Ling 24; Turman, Yidi J. 24; Topal, Michael D. 23,24; Tan, Donghui 25; Waring, Scot 24; Buda, Elizabeth 24; Walsh, Jesse 24; Jones, Corbin D. 26; Mieczkowski, Piotr A. 22; Singh, Darshan 24; Wu, Junyuan 24; Gulabani, Anisha 24; Dolina, Peter 24; Bodenheimer, Tom 24; Hoyle, Alan P. 24; Simons, Janae V. 24; Soloway, Matthew G. 24; Mose, Lisle E. 23; Jefferys, Stuart R. 23; Balu, Saianand 24; O'Connor, Brian D. 24; Prins, Jan F. 24,27; Liu, Jinze 28; Chiang, Derek Y. 22,24; Neil Hayes, D. 24,29; Perou, Charles M. 22,23,24; University of Southern CaliforniaJohns Hopkins /; Cope, Leslie 30; Danilova, Ludmila 30; Weisenberger, Daniel J. 31; Maglinte, Dennis T. 31; Pan, Fei 31; Van Den Berg, David J. 31; Triche, Timothy Jr 31; Herman, James G. 30; Baylin, Stephen B. 30; Laird, Peter W. 31; Genome data analysis centres: Broad Institute; Noble, Michael 2; Voet, Doug 2; Gehlenborg, Nils 2,14; DiCara, Daniel 2; Zhang, Jinhua 10,11; Wu, Chang-Jiun 3,11; Yingchun Liu, Spring 2; Zou, Lihua 2; Lin, Pei 2; Cho, Juok 2; Nazaire, Marc-Danie 2; Robinson, Jim 2; Thorvaldsdottir, Helga 2; Mesirov, Jill 2; Memorial Sloan-Kettering Cancer Center; Sinha, Rileen 17; Ciriello, Giovanni 17; Cerami, Ethan 17; Gross, Benjamin 17; Jacobsen, Anders 17; Gao, Jianjiong 17; Arman Aksoy, B. 17; Weinhold, Nils 17; Ramirez, Ricardo 17; Taylor, Barry S. 17; Antipin, Yevgeniy 17; Reva, Boris 17; Shen, Ronglai 32,17; Mo, Qianxing 32; Seshan, Venkatraman 32; Paik, Paul K. 33; The University of Texas MD Anderson Cancer Center; Akbani, Rehan 34; Zhang, Nianxiang 34; Broom, Bradley M. 34; Casasent, Tod 34; Unruh, Anna 34; Wakefield, Chris 34; Craig Cason, R. 35; Baggerly, Keith A. 34; Weinstein, John N. 34,36; University of California Santa CruzBuck Institute /; Haussler, David 37,38; Benz, Christopher C. 39; Stuart, Joshua M. 37; Zhu, Jingchun 37; Szeto, Christopher 37; Scott, Gary K. 39; Yau, Christina 39; Ng, Sam 37; Goldstein, Ted 37; Waltman, Peter 37; Sokolov, Artem 37; Ellrott, Kyle 37; Collisson, Eric A. 40; Zerbino, Daniel 37; Wilks, Christopher 37,31; Ma, Singer 37; Craft, Brian 37; University of North Carolina at Chapel Hill; Du, Ying 24; Cabanski, Christopher 24; Walter, Vonn 24; Marron, J. S. 41; Liu, Yufeng 25; Wang, Kai 28; Baylor College of Medicine; Creighton, Chad J. 42; Zhang, Yiqun 42; Pathology committee; Travis, William D. 43; Rekhtman, Natasha 43; Yi, Joanne 44; Aubry, Marie C. 44; Cheney, Richard 45; Dacic, Sanja 46; Flieder, Douglas 47; Funkhouser, William 48; Illei, Peter 49; Myers, Jerome 50; Tsao, Ming-Sound 51; Biospecimen core resources: International Genomics Consortium; Penny, Robert 52; Mallery, David 52; Shelton, Troy 52; Hatfield, Martha 52; Morris, Scott 52; Yena, Peggy 52; Shelton, Candace 52; Sherman, Mark 52; Paulauskis, Joseph 52; Disease working group; Govindan, Ramaswamy 53; Azodo, Ijeoma 54; Beer, David 55; Bose, Ron 53; Byers, Lauren A. 56; Carbone, David 57; Chang, Li-Wei 53; Chiang, Derek 22,24; Chun, Elizabeth 8; Collisson, Eric 40; Ding, Li 53; Heymach, John 56; Ida, Cristiane 44; Johnson, Bruce 3; Jurisica, Igor 58; Kaufman, Jacob 57; Kosari, Farhad 54; Kwiatkowski, David 3; Maher, Christopher A. 53; Mungall, Andy 8; Pao, William 57; Peifer, Martin 59,60; Robertson, Gordon 8; Rusch, Valerie 61; Siegfried, Jill 62; Stuart, Joshua 37; Thomas, Roman K. 59,60,63; Tomaszek, Sandra 54; Vaske, Charles 37; Weisenberger, Daniel 31; Wigle, Dennis A. 54; Yang, Ping 54,67; John Zhang, Jianjua 10,11; Data coordination centre; Jensen, Mark A. 65; Sfeir, Robert 65; Kahn, Ari B. 65; Chu, Anna L. 65; Kothiyal, Prachi 65; Wang, Zhining 65; Snyder, Eric E. 65; Pontius, Joan 65; Pihl, Todd D. 65; Ayala, Brenda 65; Backus, Mark 65; Walton, Jessica 65; Baboud, Julien 65; Berton, Dominique L. 65; Nicholls, Matthew C. 65; Srinivasan, Deepak 65; Raman, Rohini 65; Girshik, Stanley 65; Kigonya, Peter A. 65; Alonso, Shelley 65; Sanbhadti, Rashmi N. 65; Barletta, Sean P. 65; Greene, John M. 65; Pot, David A. 65; Tissue source sites; Bandarchi-Chamkhaleh, Bizhan 51; Boyd, Jeff 47; Weaver, JoEllen 47; Azodo, Ijeoma A. 54; Tomaszek, Sandra C. 54; Christine Aubry, Marie 66; Ida, Christiane M. 66; Brock, Malcolm V. 68; Rogers, Kristen 68; Rutledge, Marian 69; Brown, Travis 68; Lee, Beverly 69; Shin, James 70; Trusty, Dante 70; Dhir, Rajiv 71; Siegfried, Jill M. 62; Potapova, Olga 72; Fedosenko, Konstantin V. 73; Nemirovich-Danchenko, Elena 72; Zakowski, Maureen 74; Iacocca, Mary V. 75; Brown, Jennifer 75; Rabeno, Brenda 75; Czerwinski, Christine 75; Petrelli, Nicholas 75; Fan, Zhen 76; Todaro, Nicole 76; Eckman, John 50; Rathmell, Kimryn W. 24; Thorne, Leigh B. 77; Huang, Mei 77; Boice, Lori 77; Hill, Ashley 24; Curley, Erin 52; Morrison, Carl 45; Gaudioso, Carmelo 45; Bartlett, John M. S. 78; Kodeeswaran, Sugy 78; Zanke, Brent 78; Sekhon, Harman 79; David, Kerstin 80; Juhl, Hartmut 81; Van Le, Xuan 82; Kohl, Bernard 82; Thorp, Richard 82; Viet Tien, Nguyen 83; Van Bang, Nguyen 84; Sussman, Howard 85; Duc Phu, Bui 84; Hajek, Richard 86; Phi Hung, Nguyen 87; Khan, Khurram Z. 88; Muley, Thomas 89; Project team: National Cancer Institute; Mills Shaw, Kenna R. 90; Sheth, Margi 90; Yang, Liming 90; Buetow, Ken 91; Davidsen, Tanja 91; Demchok, John A. 90; Eley, Greg 91; Ferguson, Martin 92; Dillon, Laura A. L. 90; Schaefer, Carl 91; National Human Genome Research Institute; Guyer, Mark S. 93; Ozenberger, Bradley A. 93; Palchik, Jacqueline D. 93; Peterson, Jane 93; Sofia, Heidi J. 93; Thomson, Elizabeth 93; Writing committee; Johnson, Bruce E. 3
[Article]
Nature.
489(7417):519-525, September 27, 2012.
(Format: HTML, PDF)
: 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.
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