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. Mungall & 320 others Erin 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, Kenneth Buetow, 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

1943 Citations (Scopus)

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
Externally publishedYes

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Squamous Cell Neoplasms
Lung Neoplasms
Mutation
Neoplasms
Genes
Squamous Cell Carcinoma
Lung
Histocompatibility
HLA-A Antigens
Atlases
Phosphatidylinositol 3-Kinases
Epigenomics
Genome

ASJC Scopus subject areas

  • General

Cite this

Hammerman, P. S., Voet, D., Lawrence, M. S., Voet, D., Jing, R., Cibulskis, K., ... Shen, R. (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489(7417), 519-525. https://doi.org/10.1038/nature11404

Comprehensive genomic characterization of squamous cell lung cancers. / Hammerman, Peter S.; Voet, Doug; Lawrence, Michael S.; Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Sivachenko, Andrey; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Imielinski, Marcin; Helman, Elena; Hernandez, Bryan; Pho, Nam H.; Meyerson, Matthew; Chu, Andy; Hye-Chun, 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; He, An; Hirst, 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.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; 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.; Stuart, Joshua; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; O'Connor, Brian D.; Chiang, Derek; Liu, Jinze; Chiang, Derek Y.; Hayes, D. Neil; Perou, Charles M.; Cope, Leslie; Weisenberger, Daniel; 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.; Noble, Michael; Gehlenborg, Nils; DiCara, Daniel; Zhang, Jinhua; Wu, Chang Jiun; Liu, Spring Yingchun; Zou, Lihua; Lin, Pei; Cho, Juok; Nazaire, Marc Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; 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; Mo, Qianxing; Seshan, Venkatraman; Paik, Paul K.; 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; Collisson, Eric; Ellrott, Kyle; Collisson, Eric A.; Zerbino, Daniel; Ma, Singer; Craft, Brian; Du, Ying; Cabanski, Christopher; Walter, Vonn; Marron, J. S.; Liu, Yufeng; Wang, Kai; Prins, Jan F.; 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; Govindan, Ramaswamy; Azodo, Ijeoma; Beer, David; Bose, Ron; Byers, Lauren A.; Carbone, David; Chang, Li Wei; Chun, Elizabeth; Ding, Li; Heymach, John; Ida, Cristiane; Johnson, Bruce; Jurisica, Igor; Kaufman, Jacob; Kosari, Farhad; Kwiatkowski, David; Maher, Christopher A.; Mungall, Andy; Pao, William; Peifer, Martin; Robertson, Gordon; Rusch, Valerie; Siegfried, Jill; Sougnez, Carrie; Thomas, Roman K.; Tomaszek, Sandra; Vaske, Charles; Wheeler, David; Wigle, Dennis A.; Wilks, Christopher; 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.; Bandarchi-Chamkhaleh, Bizhan; Boyd, Jeff; Weaver, Joellen; Azodo, Ijeoma A.; Tomaszek, Sandra C.; Aubry, Marie Christine; Ida, Christiane M.; Yang, Ping; 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; Zakowski, Maureen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Fan, Zhen; Todaro, Nicole; Eckman, John; Rathmell, W. Kimryn; Thorne, Leigh B.; Huang, Mei; Boice, Lori; Hill, Ashley; Curley, Erin; Morrison, Carl; Gaudioso, Carmelo; Bartlett, John M S; Kodeeswaran, Sugy; Zanke, Brent; Sekhon, Harman; David, Kerstin; Juhl, Hartmut; Le, Xuan Van; Kohl, Bernard; Thorp, Richard; Tien, Nguyen Viet; Bang, Nguyen Van; Sussman, Howard; Phu, Bui Duc; Hajek, Richard; Hung, Nguyen Phi; Khan, Khurram Z.; Muley, Thomas; Mills Shaw, Kenna R.; Buetow, Kenneth; 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; Johnson, Bruce E.; Shen, Ronglai.

In: Nature, Vol. 489, No. 7417, 27.09.2012, p. 519-525.

Research output: Contribution to journalArticle

Hammerman, PS, Voet, D, Lawrence, MS, Voet, D, Jing, R, Cibulskis, K, Sivachenko, A, Stojanov, P, McKenna, A, Lander, ES, Gabriel, S, Getz, G, Imielinski, M, Helman, E, Hernandez, B, Pho, NH, Meyerson, M, Chu, A, Hye-Chun, JE, Mungall, AJ, Pleasance, E, Robertson, AG, Sipahimalani, P, Stoll, D, Balasundaram, M, Birol, I, Butterfield, YSN, Chuah, E, Coope, RJN, Corbett, R, Dhalla, N, Guin, R, He, A, Hirst, C, Hirst, M, Holt, RA, Lee, D, Li, HI, Mayo, M, Moore, RA, Mungall, K, Nip, KM, Olshen, A, Schein, JE, Slobodan, JR, Tam, A, Thiessen, N, Varhol, R, Zeng, T, Zhao, Y, Jones, SJM, Marra, MA, Saksena, G, Cherniack, AD, Schumacher, SE, Tabak, B, Carter, SL, Nguyen, H, Onofrio, RC, Crenshaw, A, Ardlie, K, Beroukhim, R, Winckler, W, Protopopov, A, Zhang, J, Hadjipanayis, A, Lee, S, Xi, R, Yang, L, Ren, X, Zhang, H, Shukla, S, Chen, PC, Haseley, P, Lee, E, Chin, L, Park, PJ, Kucherlapati, R, Socci, ND, Liang, Y, Schultz, N, Borsu, L, Lash, AE, Viale, A, Sander, C, Ladanyi, M, Auman, JT, Hoadley, KA, Wilkerson, MD, Shi, Y, Liquori, C, Meng, S, Li, L, Turman, YJ, Topal, MD, Tan, D, Waring, S, Buda, E, Walsh, J, Jones, CD, Mieczkowski, PA, Singh, D, Wu, J, Gulabani, A, Dolina, P, Bodenheimer, T, Hoyle, AP, Simons, JV, Soloway, MG, Stuart, J, Mose, LE, Jefferys, SR, Balu, S, O'Connor, BD, Chiang, D, Liu, J, Chiang, DY, Hayes, DN, Perou, CM, Cope, L, Weisenberger, D, Danilova, L, Weisenberger, DJ, Maglinte, DT, Pan, F, Van Den Berg, DJ, Triche, T, Herman, JG, Baylin, SB, Laird, PW, Noble, M, Gehlenborg, N, DiCara, D, Zhang, J, Wu, CJ, Liu, SY, Zou, L, Lin, P, Cho, J, Nazaire, MD, Robinson, J, Thorvaldsdottir, H, Mesirov, J, Sinha, R, Ciriello, G, Cerami, E, Gross, B, Jacobsen, A, Gao, J, Aksoy, BA, Weinhold, N, Ramirez, R, Taylor, BS, Antipin, Y, Reva, B, Mo, Q, Seshan, V, Paik, PK, Akbani, R, Zhang, N, Broom, BM, Casasent, T, Unruh, A, Wakefield, C, Cason, RC, Baggerly, KA, Weinstein, JN, Haussler, D, Benz, CC, Stuart, JM, Zhu, J, Szeto, C, Scott, GK, Yau, C, Ng, S, Goldstein, T, Waltman, P, Sokolov, A, Collisson, E, Ellrott, K, Collisson, EA, Zerbino, D, Ma, S, Craft, B, Du, Y, Cabanski, C, Walter, V, Marron, JS, Liu, Y, Wang, K, Prins, JF, Creighton, CJ, Zhang, Y, Travis, WD, Rekhtman, N, Yi, J, Aubry, MC, Cheney, R, Dacic, S, Flieder, D, Funkhouser, W, Illei, P, Myers, J, Tsao, MS, Penny, R, Mallery, D, Shelton, T, Hatfield, M, Morris, S, Yena, P, Shelton, C, Sherman, M, Paulauskis, J, Govindan, R, Azodo, I, Beer, D, Bose, R, Byers, LA, Carbone, D, Chang, LW, Chun, E, Ding, L, Heymach, J, Ida, C, Johnson, B, Jurisica, I, Kaufman, J, Kosari, F, Kwiatkowski, D, Maher, CA, Mungall, A, Pao, W, Peifer, M, Robertson, G, Rusch, V, Siegfried, J, Sougnez, C, Thomas, RK, Tomaszek, S, Vaske, C, Wheeler, D, Wigle, DA, Wilks, C, Zhang, JJ, Jensen, MA, Sfeir, R, Kahn, AB, Chu, AL, Kothiyal, P, Wang, Z, Snyder, EE, Pontius, J, Pihl, TD, Ayala, B, Backus, M, Walton, J, Baboud, J, Berton, DL, Nicholls, MC, Srinivasan, D, Raman, R, Girshik, S, Kigonya, PA, Alonso, S, Sanbhadti, RN, Barletta, SP, Greene, JM, Pot, DA, Bandarchi-Chamkhaleh, B, Boyd, J, Weaver, J, Azodo, IA, Tomaszek, SC, Aubry, MC, Ida, CM, Yang, P, Brock, MV, Rogers, K, Rutledge, M, Brown, T, Lee, B, Shin, J, Trusty, D, Dhir, R, Siegfried, JM, Potapova, O, Fedosenko, KV, Nemirovich-Danchenko, E, Zakowski, M, Iacocca, MV, Brown, J, Rabeno, B, Czerwinski, C, Petrelli, N, Fan, Z, Todaro, N, Eckman, J, Rathmell, WK, Thorne, LB, Huang, M, Boice, L, Hill, A, Curley, E, Morrison, C, Gaudioso, C, Bartlett, JMS, Kodeeswaran, S, Zanke, B, Sekhon, H, David, K, Juhl, H, Le, XV, Kohl, B, Thorp, R, Tien, NV, Bang, NV, Sussman, H, Phu, BD, Hajek, R, Hung, NP, Khan, KZ, Muley, T, Mills Shaw, KR, Buetow, K, Yang, L, Buetow, K, Davidsen, T, Demchok, JA, Eley, G, Ferguson, M, Dillon, LAL, Schaefer, C, Guyer, MS, Ozenberger, BA, Palchik, JD, Peterson, J, Sofia, HJ, Thomson, E, Johnson, BE & Shen, R 2012, 'Comprehensive genomic characterization of squamous cell lung cancers', Nature, vol. 489, no. 7417, pp. 519-525. https://doi.org/10.1038/nature11404
Hammerman PS, Voet D, Lawrence MS, Voet D, Jing R, Cibulskis K et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012 Sep 27;489(7417):519-525. https://doi.org/10.1038/nature11404
Hammerman, Peter S. ; Voet, Doug ; Lawrence, Michael S. ; Voet, Douglas ; Jing, Rui ; Cibulskis, Kristian ; Sivachenko, Andrey ; Stojanov, Petar ; McKenna, Aaron ; Lander, Eric S. ; Gabriel, Stacey ; Getz, Gad ; Imielinski, Marcin ; Helman, Elena ; Hernandez, Bryan ; Pho, Nam H. ; Meyerson, Matthew ; Chu, Andy ; Hye-Chun, 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 ; He, An ; Hirst, 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. ; Nguyen, Huy ; Onofrio, Robert C. ; Crenshaw, Andrew ; Ardlie, Kristin ; Beroukhim, Rameen ; Winckler, Wendy ; 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. ; Stuart, Joshua ; Mose, Lisle E. ; Jefferys, Stuart R. ; Balu, Saianand ; O'Connor, Brian D. ; Chiang, Derek ; Liu, Jinze ; Chiang, Derek Y. ; Hayes, D. Neil ; Perou, Charles M. ; Cope, Leslie ; Weisenberger, Daniel ; 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. ; Noble, Michael ; Gehlenborg, Nils ; DiCara, Daniel ; Zhang, Jinhua ; Wu, Chang Jiun ; Liu, Spring Yingchun ; Zou, Lihua ; Lin, Pei ; Cho, Juok ; Nazaire, Marc Danie ; Robinson, Jim ; Thorvaldsdottir, Helga ; Mesirov, Jill ; 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 ; Mo, Qianxing ; Seshan, Venkatraman ; Paik, Paul K. ; 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 ; Collisson, Eric ; Ellrott, Kyle ; Collisson, Eric A. ; Zerbino, Daniel ; Ma, Singer ; Craft, Brian ; Du, Ying ; Cabanski, Christopher ; Walter, Vonn ; Marron, J. S. ; Liu, Yufeng ; Wang, Kai ; Prins, Jan F. ; 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 ; Govindan, Ramaswamy ; Azodo, Ijeoma ; Beer, David ; Bose, Ron ; Byers, Lauren A. ; Carbone, David ; Chang, Li Wei ; Chun, Elizabeth ; Ding, Li ; Heymach, John ; Ida, Cristiane ; Johnson, Bruce ; Jurisica, Igor ; Kaufman, Jacob ; Kosari, Farhad ; Kwiatkowski, David ; Maher, Christopher A. ; Mungall, Andy ; Pao, William ; Peifer, Martin ; Robertson, Gordon ; Rusch, Valerie ; Siegfried, Jill ; Sougnez, Carrie ; Thomas, Roman K. ; Tomaszek, Sandra ; Vaske, Charles ; Wheeler, David ; Wigle, Dennis A. ; Wilks, Christopher ; 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. ; Bandarchi-Chamkhaleh, Bizhan ; Boyd, Jeff ; Weaver, Joellen ; Azodo, Ijeoma A. ; Tomaszek, Sandra C. ; Aubry, Marie Christine ; Ida, Christiane M. ; Yang, Ping ; 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 ; Zakowski, Maureen ; Iacocca, Mary V. ; Brown, Jennifer ; Rabeno, Brenda ; Czerwinski, Christine ; Petrelli, Nicholas ; Fan, Zhen ; Todaro, Nicole ; Eckman, John ; Rathmell, W. Kimryn ; Thorne, Leigh B. ; Huang, Mei ; Boice, Lori ; Hill, Ashley ; Curley, Erin ; Morrison, Carl ; Gaudioso, Carmelo ; Bartlett, John M S ; Kodeeswaran, Sugy ; Zanke, Brent ; Sekhon, Harman ; David, Kerstin ; Juhl, Hartmut ; Le, Xuan Van ; Kohl, Bernard ; Thorp, Richard ; Tien, Nguyen Viet ; Bang, Nguyen Van ; Sussman, Howard ; Phu, Bui Duc ; Hajek, Richard ; Hung, Nguyen Phi ; Khan, Khurram Z. ; Muley, Thomas ; Mills Shaw, Kenna R. ; Buetow, Kenneth ; 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 ; Johnson, Bruce E. ; Shen, Ronglai. / Comprehensive genomic characterization of squamous cell lung cancers. In: Nature. 2012 ; Vol. 489, No. 7417. pp. 519-525.
@article{ba1a07e2e8864a6d8d28a5ec263633ea,
title = "Comprehensive genomic characterization of squamous cell lung cancers",
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.",
author = "Hammerman, {Peter S.} and Doug Voet and Lawrence, {Michael S.} and Douglas Voet and Rui Jing and Kristian Cibulskis and Andrey Sivachenko and Petar Stojanov and Aaron McKenna and Lander, {Eric S.} and Stacey Gabriel and Gad Getz and Marcin Imielinski and Elena Helman and Bryan Hernandez and Pho, {Nam H.} and Matthew Meyerson and Andy Chu and Hye-Chun, {Jung E.} and Mungall, {Andrew J.} and Erin Pleasance and Robertson, {A. Gordon} and Payal Sipahimalani and Dominik Stoll and Miruna Balasundaram and Inanc Birol and Butterfield, {Yaron S N} and Eric Chuah and Coope, {Robin J N} and Richard Corbett and Noreen Dhalla and Ranabir Guin and An He and Carrie Hirst and Martin Hirst and Holt, {Robert A.} and Darlene Lee and Li, {Haiyan I.} and Michael Mayo and Moore, {Richard A.} and Karen Mungall and Nip, {Ka Ming} and Adam Olshen and Schein, {Jacqueline E.} and Slobodan, {Jared R.} and Angela Tam and Nina Thiessen and Richard Varhol and Thomas Zeng and Yongjun Zhao and Jones, {Steven J M} and Marra, {Marco A.} and Gordon Saksena and Cherniack, {Andrew D.} and Schumacher, {Stephen E.} and Barbara Tabak and Carter, {Scott L.} and Huy Nguyen and Onofrio, {Robert C.} and Andrew Crenshaw and Kristin Ardlie and Rameen Beroukhim and Wendy Winckler and Alexei Protopopov and Jianhua Zhang and Angela Hadjipanayis and Semin Lee and Ruibin Xi and Lixing Yang and Xiaojia Ren and Hailei Zhang and Sachet Shukla and Chen, {Peng Chieh} and Psalm Haseley and Eunjung Lee and Lynda Chin and Park, {Peter J.} and Raju Kucherlapati and Socci, {Nicholas D.} and Yupu Liang and Nikolaus Schultz and Laetitia Borsu and Lash, {Alex E.} and Agnes Viale and Chris Sander and Marc Ladanyi and Auman, {J. Todd} and Hoadley, {Katherine A.} and Wilkerson, {Matthew D.} and Yan Shi and Christina Liquori and Shaowu Meng and Ling Li and Turman, {Yidi J.} and Topal, {Michael D.} and Donghui Tan and Scot Waring and Elizabeth Buda and Jesse Walsh and Jones, {Corbin D.} and Mieczkowski, {Piotr A.} and Darshan Singh and Junyuan Wu and Anisha Gulabani and Peter Dolina and Tom Bodenheimer and Hoyle, {Alan P.} and Simons, {Janae V.} and Soloway, {Matthew G.} and Joshua Stuart and Mose, {Lisle E.} and Jefferys, {Stuart R.} and Saianand Balu and O'Connor, {Brian D.} and Derek Chiang and Jinze Liu and Chiang, {Derek Y.} and Hayes, {D. Neil} and Perou, {Charles M.} and Leslie Cope and Daniel Weisenberger and Ludmila Danilova and Weisenberger, {Daniel J.} and Maglinte, {Dennis T.} and Fei Pan and {Van Den Berg}, {David J.} and Timothy Triche and Herman, {James G.} and Baylin, {Stephen B.} and Laird, {Peter W.} and Michael Noble and Nils Gehlenborg and Daniel DiCara and Jinhua Zhang and Wu, {Chang Jiun} and Liu, {Spring Yingchun} and Lihua Zou and Pei Lin and Juok Cho and Nazaire, {Marc Danie} and Jim Robinson and Helga Thorvaldsdottir and Jill Mesirov and Rileen Sinha and Giovanni Ciriello and Ethan Cerami and Benjamin Gross and Anders Jacobsen and Jianjiong Gao and Aksoy, {B. Arman} and Nils Weinhold and Ricardo Ramirez and Taylor, {Barry S.} and Yevgeniy Antipin and Boris Reva and Qianxing Mo and Venkatraman Seshan and Paik, {Paul K.} and Rehan Akbani and Nianxiang Zhang and Broom, {Bradley M.} and Tod Casasent and Anna Unruh and Chris Wakefield and Cason, {R. Craig} and Baggerly, {Keith A.} and Weinstein, {John N.} and David Haussler and Benz, {Christopher C.} and Stuart, {Joshua M.} and Jingchun Zhu and Christopher Szeto and Scott, {Gary K.} and Christina Yau and Sam Ng and Ted Goldstein and Peter Waltman and Artem Sokolov and Eric Collisson and Kyle Ellrott and Collisson, {Eric A.} and Daniel Zerbino and Singer Ma and Brian Craft and Ying Du and Christopher Cabanski and Vonn Walter and Marron, {J. S.} and Yufeng Liu and Kai Wang and Prins, {Jan F.} and Creighton, {Chad J.} and Yiqun Zhang and Travis, {William D.} and Natasha Rekhtman and Joanne Yi and Aubry, {Marie C.} and Richard Cheney and Sanja Dacic and Douglas Flieder and William Funkhouser and Peter Illei and Jerome Myers and Tsao, {Ming Sound} and Robert Penny and David Mallery and Troy Shelton and Martha Hatfield and Scott Morris and Peggy Yena and Candace Shelton and Mark Sherman and Joseph Paulauskis and Ramaswamy Govindan and Ijeoma Azodo and David Beer and Ron Bose and Byers, {Lauren A.} and David Carbone and Chang, {Li Wei} and Elizabeth Chun and Li Ding and John Heymach and Cristiane Ida and Bruce Johnson and Igor Jurisica and Jacob Kaufman and Farhad Kosari and David Kwiatkowski and Maher, {Christopher A.} and Andy Mungall and William Pao and Martin Peifer and Gordon Robertson and Valerie Rusch and Jill Siegfried and Carrie Sougnez and Thomas, {Roman K.} and Sandra Tomaszek and Charles Vaske and David Wheeler and Wigle, {Dennis A.} and Christopher Wilks and Zhang, {Jianjua John} and Jensen, {Mark A.} and Robert Sfeir and Kahn, {Ari B.} and Chu, {Anna L.} and Prachi Kothiyal and Zhining Wang and Snyder, {Eric E.} and Joan Pontius and Pihl, {Todd D.} and Brenda Ayala and Mark Backus and Jessica Walton and Julien Baboud and Berton, {Dominique L.} and Nicholls, {Matthew C.} and Deepak Srinivasan and Rohini Raman and Stanley Girshik and Kigonya, {Peter A.} and Shelley Alonso and Sanbhadti, {Rashmi N.} and Barletta, {Sean P.} and Greene, {John M.} and Pot, {David A.} and Bizhan Bandarchi-Chamkhaleh and Jeff Boyd and Joellen Weaver and Azodo, {Ijeoma A.} and Tomaszek, {Sandra C.} and Aubry, {Marie Christine} and Ida, {Christiane M.} and Ping Yang and Brock, {Malcolm V.} and Kristen Rogers and Marian Rutledge and Travis Brown and Beverly Lee and James Shin and Dante Trusty and Rajiv Dhir and Siegfried, {Jill M.} and Olga Potapova and Fedosenko, {Konstantin V.} and Elena Nemirovich-Danchenko and Maureen Zakowski and Iacocca, {Mary V.} and Jennifer Brown and Brenda Rabeno and Christine Czerwinski and Nicholas Petrelli and Zhen Fan and Nicole Todaro and John Eckman and Rathmell, {W. Kimryn} and Thorne, {Leigh B.} and Mei Huang and Lori Boice and Ashley Hill and Erin Curley and Carl Morrison and Carmelo Gaudioso and Bartlett, {John M S} and Sugy Kodeeswaran and Brent Zanke and Harman Sekhon and Kerstin David and Hartmut Juhl and Le, {Xuan Van} and Bernard Kohl and Richard Thorp and Tien, {Nguyen Viet} and Bang, {Nguyen Van} and Howard Sussman and Phu, {Bui Duc} and Richard Hajek and Hung, {Nguyen Phi} and Khan, {Khurram Z.} and Thomas Muley and {Mills Shaw}, {Kenna R.} and Kenneth Buetow and Liming Yang and Ken Buetow and Tanja Davidsen and Demchok, {John A.} and Greg Eley and Martin Ferguson and Dillon, {Laura A L} and Carl Schaefer and Guyer, {Mark S.} and Ozenberger, {Bradley A.} and Palchik, {Jacqueline D.} and Jane Peterson and Sofia, {Heidi J.} and Elizabeth Thomson and Johnson, {Bruce E.} and Ronglai Shen",
year = "2012",
month = "9",
day = "27",
doi = "10.1038/nature11404",
language = "English (US)",
volume = "489",
pages = "519--525",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7417",

}

TY - JOUR

T1 - Comprehensive genomic characterization of squamous cell lung cancers

AU - Hammerman, Peter S.

AU - Voet, Doug

AU - Lawrence, Michael S.

AU - Voet, Douglas

AU - Jing, Rui

AU - Cibulskis, Kristian

AU - Sivachenko, Andrey

AU - Stojanov, Petar

AU - McKenna, Aaron

AU - Lander, Eric S.

AU - Gabriel, Stacey

AU - Getz, Gad

AU - Imielinski, Marcin

AU - Helman, Elena

AU - Hernandez, Bryan

AU - Pho, Nam H.

AU - Meyerson, Matthew

AU - Chu, Andy

AU - Hye-Chun, Jung E.

AU - Mungall, Andrew J.

AU - Pleasance, Erin

AU - Robertson, A. Gordon

AU - Sipahimalani, Payal

AU - Stoll, Dominik

AU - Balasundaram, Miruna

AU - Birol, Inanc

AU - Butterfield, Yaron S N

AU - Chuah, Eric

AU - Coope, Robin J N

AU - Corbett, Richard

AU - Dhalla, Noreen

AU - Guin, Ranabir

AU - He, An

AU - Hirst, Carrie

AU - Hirst, Martin

AU - Holt, Robert A.

AU - Lee, Darlene

AU - Li, Haiyan I.

AU - Mayo, Michael

AU - Moore, Richard A.

AU - Mungall, Karen

AU - Nip, Ka Ming

AU - Olshen, Adam

AU - Schein, Jacqueline E.

AU - Slobodan, Jared R.

AU - Tam, Angela

AU - Thiessen, Nina

AU - Varhol, Richard

AU - Zeng, Thomas

AU - Zhao, Yongjun

AU - Jones, Steven J M

AU - Marra, Marco A.

AU - Saksena, Gordon

AU - Cherniack, Andrew D.

AU - Schumacher, Stephen E.

AU - Tabak, Barbara

AU - Carter, Scott L.

AU - Nguyen, Huy

AU - Onofrio, Robert C.

AU - Crenshaw, Andrew

AU - Ardlie, Kristin

AU - Beroukhim, Rameen

AU - Winckler, Wendy

AU - Protopopov, Alexei

AU - Zhang, Jianhua

AU - Hadjipanayis, Angela

AU - Lee, Semin

AU - Xi, Ruibin

AU - Yang, Lixing

AU - Ren, Xiaojia

AU - Zhang, Hailei

AU - Shukla, Sachet

AU - Chen, Peng Chieh

AU - Haseley, Psalm

AU - Lee, Eunjung

AU - Chin, Lynda

AU - Park, Peter J.

AU - Kucherlapati, Raju

AU - Socci, Nicholas D.

AU - Liang, Yupu

AU - Schultz, Nikolaus

AU - Borsu, Laetitia

AU - Lash, Alex E.

AU - Viale, Agnes

AU - Sander, Chris

AU - Ladanyi, Marc

AU - Auman, J. Todd

AU - Hoadley, Katherine A.

AU - Wilkerson, Matthew D.

AU - Shi, Yan

AU - Liquori, Christina

AU - Meng, Shaowu

AU - Li, Ling

AU - Turman, Yidi J.

AU - Topal, Michael D.

AU - Tan, Donghui

AU - Waring, Scot

AU - Buda, Elizabeth

AU - Walsh, Jesse

AU - Jones, Corbin D.

AU - Mieczkowski, Piotr A.

AU - Singh, Darshan

AU - Wu, Junyuan

AU - Gulabani, Anisha

AU - Dolina, Peter

AU - Bodenheimer, Tom

AU - Hoyle, Alan P.

AU - Simons, Janae V.

AU - Soloway, Matthew G.

AU - Stuart, Joshua

AU - Mose, Lisle E.

AU - Jefferys, Stuart R.

AU - Balu, Saianand

AU - O'Connor, Brian D.

AU - Chiang, Derek

AU - Liu, Jinze

AU - Chiang, Derek Y.

AU - Hayes, D. Neil

AU - Perou, Charles M.

AU - Cope, Leslie

AU - Weisenberger, Daniel

AU - Danilova, Ludmila

AU - Weisenberger, Daniel J.

AU - Maglinte, Dennis T.

AU - Pan, Fei

AU - Van Den Berg, David J.

AU - Triche, Timothy

AU - Herman, James G.

AU - Baylin, Stephen B.

AU - Laird, Peter W.

AU - Noble, Michael

AU - Gehlenborg, Nils

AU - DiCara, Daniel

AU - Zhang, Jinhua

AU - Wu, Chang Jiun

AU - Liu, Spring Yingchun

AU - Zou, Lihua

AU - Lin, Pei

AU - Cho, Juok

AU - Nazaire, Marc Danie

AU - Robinson, Jim

AU - Thorvaldsdottir, Helga

AU - Mesirov, Jill

AU - Sinha, Rileen

AU - Ciriello, Giovanni

AU - Cerami, Ethan

AU - Gross, Benjamin

AU - Jacobsen, Anders

AU - Gao, Jianjiong

AU - Aksoy, B. Arman

AU - Weinhold, Nils

AU - Ramirez, Ricardo

AU - Taylor, Barry S.

AU - Antipin, Yevgeniy

AU - Reva, Boris

AU - Mo, Qianxing

AU - Seshan, Venkatraman

AU - Paik, Paul K.

AU - Akbani, Rehan

AU - Zhang, Nianxiang

AU - Broom, Bradley M.

AU - Casasent, Tod

AU - Unruh, Anna

AU - Wakefield, Chris

AU - Cason, R. Craig

AU - Baggerly, Keith A.

AU - Weinstein, John N.

AU - Haussler, David

AU - Benz, Christopher C.

AU - Stuart, Joshua M.

AU - Zhu, Jingchun

AU - Szeto, Christopher

AU - Scott, Gary K.

AU - Yau, Christina

AU - Ng, Sam

AU - Goldstein, Ted

AU - Waltman, Peter

AU - Sokolov, Artem

AU - Collisson, Eric

AU - Ellrott, Kyle

AU - Collisson, Eric A.

AU - Zerbino, Daniel

AU - Ma, Singer

AU - Craft, Brian

AU - Du, Ying

AU - Cabanski, Christopher

AU - Walter, Vonn

AU - Marron, J. S.

AU - Liu, Yufeng

AU - Wang, Kai

AU - Prins, Jan F.

AU - Creighton, Chad J.

AU - Zhang, Yiqun

AU - Travis, William D.

AU - Rekhtman, Natasha

AU - Yi, Joanne

AU - Aubry, Marie C.

AU - Cheney, Richard

AU - Dacic, Sanja

AU - Flieder, Douglas

AU - Funkhouser, William

AU - Illei, Peter

AU - Myers, Jerome

AU - Tsao, Ming Sound

AU - Penny, Robert

AU - Mallery, David

AU - Shelton, Troy

AU - Hatfield, Martha

AU - Morris, Scott

AU - Yena, Peggy

AU - Shelton, Candace

AU - Sherman, Mark

AU - Paulauskis, Joseph

AU - Govindan, Ramaswamy

AU - Azodo, Ijeoma

AU - Beer, David

AU - Bose, Ron

AU - Byers, Lauren A.

AU - Carbone, David

AU - Chang, Li Wei

AU - Chun, Elizabeth

AU - Ding, Li

AU - Heymach, John

AU - Ida, Cristiane

AU - Johnson, Bruce

AU - Jurisica, Igor

AU - Kaufman, Jacob

AU - Kosari, Farhad

AU - Kwiatkowski, David

AU - Maher, Christopher A.

AU - Mungall, Andy

AU - Pao, William

AU - Peifer, Martin

AU - Robertson, Gordon

AU - Rusch, Valerie

AU - Siegfried, Jill

AU - Sougnez, Carrie

AU - Thomas, Roman K.

AU - Tomaszek, Sandra

AU - Vaske, Charles

AU - Wheeler, David

AU - Wigle, Dennis A.

AU - Wilks, Christopher

AU - Zhang, Jianjua John

AU - Jensen, Mark A.

AU - Sfeir, Robert

AU - Kahn, Ari B.

AU - Chu, Anna L.

AU - Kothiyal, Prachi

AU - Wang, Zhining

AU - Snyder, Eric E.

AU - Pontius, Joan

AU - Pihl, Todd D.

AU - Ayala, Brenda

AU - Backus, Mark

AU - Walton, Jessica

AU - Baboud, Julien

AU - Berton, Dominique L.

AU - Nicholls, Matthew C.

AU - Srinivasan, Deepak

AU - Raman, Rohini

AU - Girshik, Stanley

AU - Kigonya, Peter A.

AU - Alonso, Shelley

AU - Sanbhadti, Rashmi N.

AU - Barletta, Sean P.

AU - Greene, John M.

AU - Pot, David A.

AU - Bandarchi-Chamkhaleh, Bizhan

AU - Boyd, Jeff

AU - Weaver, Joellen

AU - Azodo, Ijeoma A.

AU - Tomaszek, Sandra C.

AU - Aubry, Marie Christine

AU - Ida, Christiane M.

AU - Yang, Ping

AU - Brock, Malcolm V.

AU - Rogers, Kristen

AU - Rutledge, Marian

AU - Brown, Travis

AU - Lee, Beverly

AU - Shin, James

AU - Trusty, Dante

AU - Dhir, Rajiv

AU - Siegfried, Jill M.

AU - Potapova, Olga

AU - Fedosenko, Konstantin V.

AU - Nemirovich-Danchenko, Elena

AU - Zakowski, Maureen

AU - Iacocca, Mary V.

AU - Brown, Jennifer

AU - Rabeno, Brenda

AU - Czerwinski, Christine

AU - Petrelli, Nicholas

AU - Fan, Zhen

AU - Todaro, Nicole

AU - Eckman, John

AU - Rathmell, W. Kimryn

AU - Thorne, Leigh B.

AU - Huang, Mei

AU - Boice, Lori

AU - Hill, Ashley

AU - Curley, Erin

AU - Morrison, Carl

AU - Gaudioso, Carmelo

AU - Bartlett, John M S

AU - Kodeeswaran, Sugy

AU - Zanke, Brent

AU - Sekhon, Harman

AU - David, Kerstin

AU - Juhl, Hartmut

AU - Le, Xuan Van

AU - Kohl, Bernard

AU - Thorp, Richard

AU - Tien, Nguyen Viet

AU - Bang, Nguyen Van

AU - Sussman, Howard

AU - Phu, Bui Duc

AU - Hajek, Richard

AU - Hung, Nguyen Phi

AU - Khan, Khurram Z.

AU - Muley, Thomas

AU - Mills Shaw, Kenna R.

AU - Buetow, Kenneth

AU - Yang, Liming

AU - Buetow, Ken

AU - Davidsen, Tanja

AU - Demchok, John A.

AU - Eley, Greg

AU - Ferguson, Martin

AU - Dillon, Laura A L

AU - Schaefer, Carl

AU - Guyer, Mark S.

AU - Ozenberger, Bradley A.

AU - Palchik, Jacqueline D.

AU - Peterson, Jane

AU - Sofia, Heidi J.

AU - Thomson, Elizabeth

AU - Johnson, Bruce E.

AU - Shen, Ronglai

PY - 2012/9/27

Y1 - 2012/9/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84866894408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866894408&partnerID=8YFLogxK

U2 - 10.1038/nature11404

DO - 10.1038/nature11404

M3 - Article

VL - 489

SP - 519

EP - 525

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7417

ER -