Comprehensive molecular profiling of lung adenocarcinoma

The cancer genome atlas research network

Eric A. Collisson, Joshua D. Campbell, Angela N. Brooks, Alice H. Berger, William Lee, Juliann Chmielecki, David G. Beer, Leslie Cope, Chad J. Creighton, Ludmila Danilova, Li Ding, Gad Getz, Peter S. Hammerman, D. Neil Hayes, Bryan Hernandez, James G. Herman, John V. Heymach, Igor Jurisica, Raju Kucherlapati, David Kwiatkowski & 290 others Marc Ladanyi, Gordon Robertson, Nikolaus Schultz, Ronglai Shen, Rileen Sinha, Carrie Sougnez, Ming Sound Tsao, William D. Travis, John N. Weinstein, Dennis A. Wigle, Matthew D. Wilkerson, Andy Chu, Andrew D. Cherniack, Angela Hadjipanayis, Mara Rosenberg, Daniel J. Weisenberger, Peter W. Laird, Amie Radenbaugh, Singer Ma, Joshua M. Stuart, Lauren Averett Byers, Stephen B. Baylin, Ramaswamy Govindan, Matthew Meyerson, Stacey B. Gabriel, Kristian Cibulskis, Jaegil Kim, Chip Stewart, Lee Lichtenstein, Eric S. Lander, Michael S. Lawrence, E. Getz, Robert Fulton, Lucinda L. Fulton, Michael D. McLellan, Richard K. Wilson, Kai Ye, Catrina C. Fronick, Christopher A. Maher, Christopher A. Miller, Michael C. Wendl, Christopher Cabanski, Elaine Mardis, David Wheeler, Miruna Balasundaram, Yaron S N Butterfield, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Ranabir Guin, Carrie Hirst, Darlene Lee, Haiyan I. Li, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Richard Varhol, A. Gordon Robertson, Natasja Wye, Nina Thiessen, Robert A. Holt, Steven J M Jones, Marco A. Marra, Marcin Imielinski, Robert C. Onofrio, Eran Hodis, Travis Zack, Elena Helman, Chandra Sekhar Pedamallu, Jill Mesirov, Gordon Saksena, Steven E. Schumacher, Scott L. Carter, Levi Garraway, Rameen Beroukhim, Semin Lee, Harshad S. Mahadeshwar, Angeliki Pantazi, Alexei Protopopov, Xiaojia Ren, Sahil Seth, Xingzhi Song, Jiabin Tang, Lixing Yang, Jianhua Zhang, Peng Chieh Chen, Michael Parfenov, Andrew Wei Xu, Netty Santoso, Lynda Chin, Peter J. Park, Katherine A. Hoadley, J. Todd Auman, Shaowu Meng, Yan Shi, Elizabeth Buda, Scot Waring, Umadevi Veluvolu, Donghui Tan, Piotr A. Mieczkowski, Corbin D. Jones, Janae V. Simons, Matthew G. Soloway, Tom Bodenheimer, Stuart R. Jefferys, Jeffrey Roach, Alan P. Hoyle, Junyuan Wu, Saianand Balu, Darshan Singh, Jan F. Prins, J. S. Marron, Joel S. Parker, Charles M. Perou, Jinze Liu, Dennis T. Maglinte, Philip H. Lai, Moiz S. Bootwalla, David J. Van Den Berg, Timothy Triche, Juok Cho, Daniel DiCara, David Heiman, Pei Lin, William Mallard, Douglas Voet, Hailei Zhang, Lihua Zou, Michael S. Noble, Nils Gehlenborg, Helga Thorvaldsdottir, Marc Danie Nazaire, Jim Robinson, B. Arman Aksoy, Giovanni Ciriello, Barry S. Taylor, Gideon Dresdner, Jianjiong Gao, Benjamin Gross, Venkatraman E. Seshan, Boris Reva, S. Onur Sumer, Nils Weinhold, Chris Sander, Sam Ng, Jingchun Zhu, Christopher C. Benz, Christina Yau, David Haussler, Paul T. Spellman, Patrick K. Kimes, Bradley M. Broom, Jing Wang, Yiling Lu, Patrick Kwok Shing Ng, Lixia Diao, Wenbin Liu, Christopher I. Amos, Rehan Akbani, Gordon B. Mills, Erin Curley, Joseph Paulauskis, Kevin Lau, Scott Morris, Troy Shelton, David Mallery, Johanna Gardner, Robert Penny, Charles Saller, Katherine Tarvin, William G. Richards, Robert Cerfolio, Ayesha Bryant, Daniel P. Raymond, Nathan A. Pennell, Carol Farver, Christine Czerwinski, Lori Huelsenbeck-Dill, Mary Iacocca, Nicholas Petrelli, Brenda Rabeno, Jennifer Brown, Thomas Bauer, Cureline Oleg Dolzhanskiy, Olga Potapova, Daniil Rotin, Olga Voronina, Elena Nemirovich-Danchenko, Konstantin V. Fedosenko, Anthony Gal, Madhusmita Behera, Suresh S. Ramalingam, Gabriel Sica, Douglas Flieder, Jeff Boyd, Jo Ellen Weaver, Bernard Kohl, Dang Huy Quoc Thinh, George Sandusky, Hartmut Juhl, Edwina Duhig, Peter Illei, Edward Gabrielson, James Shin, Beverly Lee, Kristen Rogers, Dante Trusty, Malcolm V. Brock, Christina Williamson, Eric Burks, Kimberly Rieger-Christ, Antonia Holway, Travis Sullivan, Michael K. Asiedu, Farhad Kosari, Natasha Rekhtman, Maureen Zakowski, Valerie W. Rusch, Paul Zippile, James Suh, Harvey Pass, Chandra Goparaju, Yvonne Owusu-Sarpong, John M S Bartlett, Sugy Kodeeswaran, Jeremy Parfitt, Harmanjatinder Sekhon, Monique Albert, John Eckman, Jerome B. Myers, Carl Morrison, Carmelo Gaudioso, Jeffrey A. Borgia, Philip Bonomi, Mark Pool, Michael J. Liptay, Fedor Moiseenko, Irina Zaytseva, Hendrik Dienemann, Michael Meister, Philipp A. Schnabel, Thomas R. Muley, Martin Peifer, Carmen Gomez-Fernandez, Lynn Herbert, Sophie Egea, Mei Huang, Leigh B. Thorne, Lori Boice, Ashley Hill Salazar, William K. Funkhouser, W. Kimryn Rathmell, Rajiv Dhir, Samuel A. Yousem, Sanja Dacic, Frank Schneider, Jill M. Siegfried, Richard Hajek, Mark A. Watson, Sandra McDonald, Bryan Meyers, Belinda Clarke, Ian A. Yang, Kwun M. Fong, Lindy Hunter, Morgan Windsor, Rayleen V. Bowman, Solange Peters, Igor Letovanec, Khurram Z. Khan, Mark A. Jensen, Eric E. Snyder, Deepak Srinivasan, Ari B. Kahn, Julien Baboud, David A. Pot, Kenna R Mills Shaw, Margi Sheth, Tanja Davidsen, John A. Demchok, Liming Yang, Zhining Wang, Roy Tarnuzzer, Jean Claude Zenklusen, Bradley A. Ozenberger, Heidi J. Sofia, Richard Cheney

Research output: Contribution to journalArticle

1656 Citations (Scopus)

Abstract

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Original languageEnglish
Pages (from-to)543-550
Number of pages8
JournalNature
Volume511
Issue number7511
DOIs
StatePublished - 2014

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Atlases
Genome
Mutation
Research
Neoplasms
Messenger RNA
RNA Sequence Analysis
Mutation Rate
MicroRNAs
DNA Sequence Analysis
Oncogenes
Proteomics
Methylation
Adenocarcinoma of lung
Cause of Death
Exons
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Collisson, E. A., Campbell, J. D., Brooks, A. N., Berger, A. H., Lee, W., Chmielecki, J., ... Cheney, R. (2014). Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network. Nature, 511(7511), 543-550. https://doi.org/10.1038/nature13385

Comprehensive molecular profiling of lung adenocarcinoma : The cancer genome atlas research network. / Collisson, Eric A.; Campbell, Joshua D.; Brooks, Angela N.; Berger, Alice H.; Lee, William; Chmielecki, Juliann; Beer, David G.; Cope, Leslie; Creighton, Chad J.; Danilova, Ludmila; Ding, Li; Getz, Gad; Hammerman, Peter S.; Hayes, D. Neil; Hernandez, Bryan; Herman, James G.; Heymach, John V.; Jurisica, Igor; Kucherlapati, Raju; Kwiatkowski, David; Ladanyi, Marc; Robertson, Gordon; Schultz, Nikolaus; Shen, Ronglai; Sinha, Rileen; Sougnez, Carrie; Tsao, Ming Sound; Travis, William D.; Weinstein, John N.; Wigle, Dennis A.; Wilkerson, Matthew D.; Chu, Andy; Cherniack, Andrew D.; Hadjipanayis, Angela; Rosenberg, Mara; Weisenberger, Daniel J.; Laird, Peter W.; Radenbaugh, Amie; Ma, Singer; Stuart, Joshua M.; Byers, Lauren Averett; Baylin, Stephen B.; Govindan, Ramaswamy; Meyerson, Matthew; Gabriel, Stacey B.; Cibulskis, Kristian; Kim, Jaegil; Stewart, Chip; Lichtenstein, Lee; Lander, Eric S.; Lawrence, Michael S.; Getz, E.; Fulton, Robert; Fulton, Lucinda L.; McLellan, Michael D.; Wilson, Richard K.; Ye, Kai; Fronick, Catrina C.; Maher, Christopher A.; Miller, Christopher A.; Wendl, Michael C.; Cabanski, Christopher; Mardis, Elaine; Wheeler, David; Balasundaram, Miruna; Butterfield, Yaron S N; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Varhol, Richard; Robertson, A. Gordon; Wye, Natasja; Thiessen, Nina; Holt, Robert A.; Jones, Steven J M; Marra, Marco A.; Imielinski, Marcin; Onofrio, Robert C.; Hodis, Eran; Zack, Travis; Helman, Elena; Pedamallu, Chandra Sekhar; Mesirov, Jill; Saksena, Gordon; Schumacher, Steven E.; Carter, Scott L.; Garraway, Levi; Beroukhim, Rameen; Lee, Semin; Mahadeshwar, Harshad S.; Pantazi, Angeliki; Protopopov, Alexei; Ren, Xiaojia; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Yang, Lixing; Zhang, Jianhua; Chen, Peng Chieh; Parfenov, Michael; Xu, Andrew Wei; Santoso, Netty; Chin, Lynda; Park, Peter J.; Hoadley, Katherine A.; Auman, J. Todd; Meng, Shaowu; Shi, Yan; Buda, Elizabeth; Waring, Scot; Veluvolu, Umadevi; Tan, Donghui; Mieczkowski, Piotr A.; Jones, Corbin D.; Simons, Janae V.; Soloway, Matthew G.; Bodenheimer, Tom; Jefferys, Stuart R.; Roach, Jeffrey; Hoyle, Alan P.; Wu, Junyuan; Balu, Saianand; Singh, Darshan; Prins, Jan F.; Marron, J. S.; Parker, Joel S.; Perou, Charles M.; Liu, Jinze; Maglinte, Dennis T.; Lai, Philip H.; Bootwalla, Moiz S.; Van Den Berg, David J.; Triche, Timothy; Cho, Juok; DiCara, Daniel; Heiman, David; Lin, Pei; Mallard, William; Voet, Douglas; Zhang, Hailei; Zou, Lihua; Noble, Michael S.; Gehlenborg, Nils; Thorvaldsdottir, Helga; Nazaire, Marc Danie; Robinson, Jim; Aksoy, B. Arman; Ciriello, Giovanni; Taylor, Barry S.; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Seshan, Venkatraman E.; Reva, Boris; Sumer, S. Onur; Weinhold, Nils; Sander, Chris; Ng, Sam; Zhu, Jingchun; Benz, Christopher C.; Yau, Christina; Haussler, David; Spellman, Paul T.; Kimes, Patrick K.; Broom, Bradley M.; Wang, Jing; Lu, Yiling; Ng, Patrick Kwok Shing; Diao, Lixia; Liu, Wenbin; Amos, Christopher I.; Akbani, Rehan; Mills, Gordon B.; Curley, Erin; Paulauskis, Joseph; Lau, Kevin; Morris, Scott; Shelton, Troy; Mallery, David; Gardner, Johanna; Penny, Robert; Saller, Charles; Tarvin, Katherine; Richards, William G.; Cerfolio, Robert; Bryant, Ayesha; Raymond, Daniel P.; Pennell, Nathan A.; Farver, Carol; Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Rabeno, Brenda; Brown, Jennifer; Bauer, Thomas; Dolzhanskiy, Cureline Oleg; Potapova, Olga; Rotin, Daniil; Voronina, Olga; Nemirovich-Danchenko, Elena; Fedosenko, Konstantin V.; Gal, Anthony; Behera, Madhusmita; Ramalingam, Suresh S.; Sica, Gabriel; Flieder, Douglas; Boyd, Jeff; Weaver, Jo Ellen; Kohl, Bernard; Thinh, Dang Huy Quoc; Sandusky, George; Juhl, Hartmut; Duhig, Edwina; Illei, Peter; Gabrielson, Edward; Shin, James; Lee, Beverly; Rogers, Kristen; Trusty, Dante; Brock, Malcolm V.; Williamson, Christina; Burks, Eric; Rieger-Christ, Kimberly; Holway, Antonia; Sullivan, Travis; Asiedu, Michael K.; Kosari, Farhad; Rekhtman, Natasha; Zakowski, Maureen; Rusch, Valerie W.; Zippile, Paul; Suh, James; Pass, Harvey; Goparaju, Chandra; Owusu-Sarpong, Yvonne; Bartlett, John M S; Kodeeswaran, Sugy; Parfitt, Jeremy; Sekhon, Harmanjatinder; Albert, Monique; Eckman, John; Myers, Jerome B.; Morrison, Carl; Gaudioso, Carmelo; Borgia, Jeffrey A.; Bonomi, Philip; Pool, Mark; Liptay, Michael J.; Moiseenko, Fedor; Zaytseva, Irina; Dienemann, Hendrik; Meister, Michael; Schnabel, Philipp A.; Muley, Thomas R.; Peifer, Martin; Gomez-Fernandez, Carmen; Herbert, Lynn; Egea, Sophie; Huang, Mei; Thorne, Leigh B.; Boice, Lori; Salazar, Ashley Hill; Funkhouser, William K.; Rathmell, W. Kimryn; Dhir, Rajiv; Yousem, Samuel A.; Dacic, Sanja; Schneider, Frank; Siegfried, Jill M.; Hajek, Richard; Watson, Mark A.; McDonald, Sandra; Meyers, Bryan; Clarke, Belinda; Yang, Ian A.; Fong, Kwun M.; Hunter, Lindy; Windsor, Morgan; Bowman, Rayleen V.; Peters, Solange; Letovanec, Igor; Khan, Khurram Z.; Jensen, Mark A.; Snyder, Eric E.; Srinivasan, Deepak; Kahn, Ari B.; Baboud, Julien; Pot, David A.; Shaw, Kenna R Mills; Sheth, Margi; Davidsen, Tanja; Demchok, John A.; Yang, Liming; Wang, Zhining; Tarnuzzer, Roy; Zenklusen, Jean Claude; Ozenberger, Bradley A.; Sofia, Heidi J.; Cheney, Richard.

In: Nature, Vol. 511, No. 7511, 2014, p. 543-550.

Research output: Contribution to journalArticle

Collisson, EA, Campbell, JD, Brooks, AN, Berger, AH, Lee, W, Chmielecki, J, Beer, DG, Cope, L, Creighton, CJ, Danilova, L, Ding, L, Getz, G, Hammerman, PS, Hayes, DN, Hernandez, B, Herman, JG, Heymach, JV, Jurisica, I, Kucherlapati, R, Kwiatkowski, D, Ladanyi, M, Robertson, G, Schultz, N, Shen, R, Sinha, R, Sougnez, C, Tsao, MS, Travis, WD, Weinstein, JN, Wigle, DA, Wilkerson, MD, Chu, A, Cherniack, AD, Hadjipanayis, A, Rosenberg, M, Weisenberger, DJ, Laird, PW, Radenbaugh, A, Ma, S, Stuart, JM, Byers, LA, Baylin, SB, Govindan, R, Meyerson, M, Gabriel, SB, Cibulskis, K, Kim, J, Stewart, C, Lichtenstein, L, Lander, ES, Lawrence, MS, Getz, E, Fulton, R, Fulton, LL, McLellan, MD, Wilson, RK, Ye, K, Fronick, CC, Maher, CA, Miller, CA, Wendl, MC, Cabanski, C, Mardis, E, Wheeler, D, Balasundaram, M, Butterfield, YSN, Carlsen, R, Chuah, E, Dhalla, N, Guin, R, Hirst, C, Lee, D, Li, HI, Mayo, M, Moore, RA, Mungall, AJ, Schein, JE, Sipahimalani, P, Tam, A, Varhol, R, Robertson, AG, Wye, N, Thiessen, N, Holt, RA, Jones, SJM, Marra, MA, Imielinski, M, Onofrio, RC, Hodis, E, Zack, T, Helman, E, Pedamallu, CS, Mesirov, J, Saksena, G, Schumacher, SE, Carter, SL, Garraway, L, Beroukhim, R, Lee, S, Mahadeshwar, HS, Pantazi, A, Protopopov, A, Ren, X, Seth, S, Song, X, Tang, J, Yang, L, Zhang, J, Chen, PC, Parfenov, M, Xu, AW, Santoso, N, Chin, L, Park, PJ, Hoadley, KA, Auman, JT, Meng, S, Shi, Y, Buda, E, Waring, S, Veluvolu, U, Tan, D, Mieczkowski, PA, Jones, CD, Simons, JV, Soloway, MG, Bodenheimer, T, Jefferys, SR, Roach, J, Hoyle, AP, Wu, J, Balu, S, Singh, D, Prins, JF, Marron, JS, Parker, JS, Perou, CM, Liu, J, Maglinte, DT, Lai, PH, Bootwalla, MS, Van Den Berg, DJ, Triche, T, Cho, J, DiCara, D, Heiman, D, Lin, P, Mallard, W, Voet, D, Zhang, H, Zou, L, Noble, MS, Gehlenborg, N, Thorvaldsdottir, H, Nazaire, MD, Robinson, J, Aksoy, BA, Ciriello, G, Taylor, BS, Dresdner, G, Gao, J, Gross, B, Seshan, VE, Reva, B, Sumer, SO, Weinhold, N, Sander, C, Ng, S, Zhu, J, Benz, CC, Yau, C, Haussler, D, Spellman, PT, Kimes, PK, Broom, BM, Wang, J, Lu, Y, Ng, PKS, Diao, L, Liu, W, Amos, CI, Akbani, R, Mills, GB, Curley, E, Paulauskis, J, Lau, K, Morris, S, Shelton, T, Mallery, D, Gardner, J, Penny, R, Saller, C, Tarvin, K, Richards, WG, Cerfolio, R, Bryant, A, Raymond, DP, Pennell, NA, Farver, C, Czerwinski, C, Huelsenbeck-Dill, L, Iacocca, M, Petrelli, N, Rabeno, B, Brown, J, Bauer, T, Dolzhanskiy, CO, Potapova, O, Rotin, D, Voronina, O, Nemirovich-Danchenko, E, Fedosenko, KV, Gal, A, Behera, M, Ramalingam, SS, Sica, G, Flieder, D, Boyd, J, Weaver, JE, Kohl, B, Thinh, DHQ, Sandusky, G, Juhl, H, Duhig, E, Illei, P, Gabrielson, E, Shin, J, Lee, B, Rogers, K, Trusty, D, Brock, MV, Williamson, C, Burks, E, Rieger-Christ, K, Holway, A, Sullivan, T, Asiedu, MK, Kosari, F, Rekhtman, N, Zakowski, M, Rusch, VW, Zippile, P, Suh, J, Pass, H, Goparaju, C, Owusu-Sarpong, Y, Bartlett, JMS, Kodeeswaran, S, Parfitt, J, Sekhon, H, Albert, M, Eckman, J, Myers, JB, Morrison, C, Gaudioso, C, Borgia, JA, Bonomi, P, Pool, M, Liptay, MJ, Moiseenko, F, Zaytseva, I, Dienemann, H, Meister, M, Schnabel, PA, Muley, TR, Peifer, M, Gomez-Fernandez, C, Herbert, L, Egea, S, Huang, M, Thorne, LB, Boice, L, Salazar, AH, Funkhouser, WK, Rathmell, WK, Dhir, R, Yousem, SA, Dacic, S, Schneider, F, Siegfried, JM, Hajek, R, Watson, MA, McDonald, S, Meyers, B, Clarke, B, Yang, IA, Fong, KM, Hunter, L, Windsor, M, Bowman, RV, Peters, S, Letovanec, I, Khan, KZ, Jensen, MA, Snyder, EE, Srinivasan, D, Kahn, AB, Baboud, J, Pot, DA, Shaw, KRM, Sheth, M, Davidsen, T, Demchok, JA, Yang, L, Wang, Z, Tarnuzzer, R, Zenklusen, JC, Ozenberger, BA, Sofia, HJ & Cheney, R 2014, 'Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network', Nature, vol. 511, no. 7511, pp. 543-550. https://doi.org/10.1038/nature13385
Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J et al. Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network. Nature. 2014;511(7511):543-550. https://doi.org/10.1038/nature13385
Collisson, Eric A. ; Campbell, Joshua D. ; Brooks, Angela N. ; Berger, Alice H. ; Lee, William ; Chmielecki, Juliann ; Beer, David G. ; Cope, Leslie ; Creighton, Chad J. ; Danilova, Ludmila ; Ding, Li ; Getz, Gad ; Hammerman, Peter S. ; Hayes, D. Neil ; Hernandez, Bryan ; Herman, James G. ; Heymach, John V. ; Jurisica, Igor ; Kucherlapati, Raju ; Kwiatkowski, David ; Ladanyi, Marc ; Robertson, Gordon ; Schultz, Nikolaus ; Shen, Ronglai ; Sinha, Rileen ; Sougnez, Carrie ; Tsao, Ming Sound ; Travis, William D. ; Weinstein, John N. ; Wigle, Dennis A. ; Wilkerson, Matthew D. ; Chu, Andy ; Cherniack, Andrew D. ; Hadjipanayis, Angela ; Rosenberg, Mara ; Weisenberger, Daniel J. ; Laird, Peter W. ; Radenbaugh, Amie ; Ma, Singer ; Stuart, Joshua M. ; Byers, Lauren Averett ; Baylin, Stephen B. ; Govindan, Ramaswamy ; Meyerson, Matthew ; Gabriel, Stacey B. ; Cibulskis, Kristian ; Kim, Jaegil ; Stewart, Chip ; Lichtenstein, Lee ; Lander, Eric S. ; Lawrence, Michael S. ; Getz, E. ; Fulton, Robert ; Fulton, Lucinda L. ; McLellan, Michael D. ; Wilson, Richard K. ; Ye, Kai ; Fronick, Catrina C. ; Maher, Christopher A. ; Miller, Christopher A. ; Wendl, Michael C. ; Cabanski, Christopher ; Mardis, Elaine ; Wheeler, David ; Balasundaram, Miruna ; Butterfield, Yaron S N ; Carlsen, Rebecca ; Chuah, Eric ; Dhalla, Noreen ; Guin, Ranabir ; Hirst, Carrie ; Lee, Darlene ; Li, Haiyan I. ; Mayo, Michael ; Moore, Richard A. ; Mungall, Andrew J. ; Schein, Jacqueline E. ; Sipahimalani, Payal ; Tam, Angela ; Varhol, Richard ; Robertson, A. Gordon ; Wye, Natasja ; Thiessen, Nina ; Holt, Robert A. ; Jones, Steven J M ; Marra, Marco A. ; Imielinski, Marcin ; Onofrio, Robert C. ; Hodis, Eran ; Zack, Travis ; Helman, Elena ; Pedamallu, Chandra Sekhar ; Mesirov, Jill ; Saksena, Gordon ; Schumacher, Steven E. ; Carter, Scott L. ; Garraway, Levi ; Beroukhim, Rameen ; Lee, Semin ; Mahadeshwar, Harshad S. ; Pantazi, Angeliki ; Protopopov, Alexei ; Ren, Xiaojia ; Seth, Sahil ; Song, Xingzhi ; Tang, Jiabin ; Yang, Lixing ; Zhang, Jianhua ; Chen, Peng Chieh ; Parfenov, Michael ; Xu, Andrew Wei ; Santoso, Netty ; Chin, Lynda ; Park, Peter J. ; Hoadley, Katherine A. ; Auman, J. Todd ; Meng, Shaowu ; Shi, Yan ; Buda, Elizabeth ; Waring, Scot ; Veluvolu, Umadevi ; Tan, Donghui ; Mieczkowski, Piotr A. ; Jones, Corbin D. ; Simons, Janae V. ; Soloway, Matthew G. ; Bodenheimer, Tom ; Jefferys, Stuart R. ; Roach, Jeffrey ; Hoyle, Alan P. ; Wu, Junyuan ; Balu, Saianand ; Singh, Darshan ; Prins, Jan F. ; Marron, J. S. ; Parker, Joel S. ; Perou, Charles M. ; Liu, Jinze ; Maglinte, Dennis T. ; Lai, Philip H. ; Bootwalla, Moiz S. ; Van Den Berg, David J. ; Triche, Timothy ; Cho, Juok ; DiCara, Daniel ; Heiman, David ; Lin, Pei ; Mallard, William ; Voet, Douglas ; Zhang, Hailei ; Zou, Lihua ; Noble, Michael S. ; Gehlenborg, Nils ; Thorvaldsdottir, Helga ; Nazaire, Marc Danie ; Robinson, Jim ; Aksoy, B. Arman ; Ciriello, Giovanni ; Taylor, Barry S. ; Dresdner, Gideon ; Gao, Jianjiong ; Gross, Benjamin ; Seshan, Venkatraman E. ; Reva, Boris ; Sumer, S. Onur ; Weinhold, Nils ; Sander, Chris ; Ng, Sam ; Zhu, Jingchun ; Benz, Christopher C. ; Yau, Christina ; Haussler, David ; Spellman, Paul T. ; Kimes, Patrick K. ; Broom, Bradley M. ; Wang, Jing ; Lu, Yiling ; Ng, Patrick Kwok Shing ; Diao, Lixia ; Liu, Wenbin ; Amos, Christopher I. ; Akbani, Rehan ; Mills, Gordon B. ; Curley, Erin ; Paulauskis, Joseph ; Lau, Kevin ; Morris, Scott ; Shelton, Troy ; Mallery, David ; Gardner, Johanna ; Penny, Robert ; Saller, Charles ; Tarvin, Katherine ; Richards, William G. ; Cerfolio, Robert ; Bryant, Ayesha ; Raymond, Daniel P. ; Pennell, Nathan A. ; Farver, Carol ; Czerwinski, Christine ; Huelsenbeck-Dill, Lori ; Iacocca, Mary ; Petrelli, Nicholas ; Rabeno, Brenda ; Brown, Jennifer ; Bauer, Thomas ; Dolzhanskiy, Cureline Oleg ; Potapova, Olga ; Rotin, Daniil ; Voronina, Olga ; Nemirovich-Danchenko, Elena ; Fedosenko, Konstantin V. ; Gal, Anthony ; Behera, Madhusmita ; Ramalingam, Suresh S. ; Sica, Gabriel ; Flieder, Douglas ; Boyd, Jeff ; Weaver, Jo Ellen ; Kohl, Bernard ; Thinh, Dang Huy Quoc ; Sandusky, George ; Juhl, Hartmut ; Duhig, Edwina ; Illei, Peter ; Gabrielson, Edward ; Shin, James ; Lee, Beverly ; Rogers, Kristen ; Trusty, Dante ; Brock, Malcolm V. ; Williamson, Christina ; Burks, Eric ; Rieger-Christ, Kimberly ; Holway, Antonia ; Sullivan, Travis ; Asiedu, Michael K. ; Kosari, Farhad ; Rekhtman, Natasha ; Zakowski, Maureen ; Rusch, Valerie W. ; Zippile, Paul ; Suh, James ; Pass, Harvey ; Goparaju, Chandra ; Owusu-Sarpong, Yvonne ; Bartlett, John M S ; Kodeeswaran, Sugy ; Parfitt, Jeremy ; Sekhon, Harmanjatinder ; Albert, Monique ; Eckman, John ; Myers, Jerome B. ; Morrison, Carl ; Gaudioso, Carmelo ; Borgia, Jeffrey A. ; Bonomi, Philip ; Pool, Mark ; Liptay, Michael J. ; Moiseenko, Fedor ; Zaytseva, Irina ; Dienemann, Hendrik ; Meister, Michael ; Schnabel, Philipp A. ; Muley, Thomas R. ; Peifer, Martin ; Gomez-Fernandez, Carmen ; Herbert, Lynn ; Egea, Sophie ; Huang, Mei ; Thorne, Leigh B. ; Boice, Lori ; Salazar, Ashley Hill ; Funkhouser, William K. ; Rathmell, W. Kimryn ; Dhir, Rajiv ; Yousem, Samuel A. ; Dacic, Sanja ; Schneider, Frank ; Siegfried, Jill M. ; Hajek, Richard ; Watson, Mark A. ; McDonald, Sandra ; Meyers, Bryan ; Clarke, Belinda ; Yang, Ian A. ; Fong, Kwun M. ; Hunter, Lindy ; Windsor, Morgan ; Bowman, Rayleen V. ; Peters, Solange ; Letovanec, Igor ; Khan, Khurram Z. ; Jensen, Mark A. ; Snyder, Eric E. ; Srinivasan, Deepak ; Kahn, Ari B. ; Baboud, Julien ; Pot, David A. ; Shaw, Kenna R Mills ; Sheth, Margi ; Davidsen, Tanja ; Demchok, John A. ; Yang, Liming ; Wang, Zhining ; Tarnuzzer, Roy ; Zenklusen, Jean Claude ; Ozenberger, Bradley A. ; Sofia, Heidi J. ; Cheney, Richard. / Comprehensive molecular profiling of lung adenocarcinoma : The cancer genome atlas research network. In: Nature. 2014 ; Vol. 511, No. 7511. pp. 543-550.
@article{618e25fe509d4c459ce82d6d591b70a4,
title = "Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network",
abstract = "Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13{\%} of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4{\%} of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.",
author = "Collisson, {Eric A.} and Campbell, {Joshua D.} and Brooks, {Angela N.} and Berger, {Alice H.} and William Lee and Juliann Chmielecki and Beer, {David G.} and Leslie Cope and Creighton, {Chad J.} and Ludmila Danilova and Li Ding and Gad Getz and Hammerman, {Peter S.} and Hayes, {D. Neil} and Bryan Hernandez and Herman, {James G.} and Heymach, {John V.} and Igor Jurisica and Raju Kucherlapati and David Kwiatkowski and Marc Ladanyi and Gordon Robertson and Nikolaus Schultz and Ronglai Shen and Rileen Sinha and Carrie Sougnez and Tsao, {Ming Sound} and Travis, {William D.} and Weinstein, {John N.} and Wigle, {Dennis A.} and Wilkerson, {Matthew D.} and Andy Chu and Cherniack, {Andrew D.} and Angela Hadjipanayis and Mara Rosenberg and Weisenberger, {Daniel J.} and Laird, {Peter W.} and Amie Radenbaugh and Singer Ma and Stuart, {Joshua M.} and Byers, {Lauren Averett} and Baylin, {Stephen B.} and Ramaswamy Govindan and Matthew Meyerson and Gabriel, {Stacey B.} and Kristian Cibulskis and Jaegil Kim and Chip Stewart and Lee Lichtenstein and Lander, {Eric S.} and Lawrence, {Michael S.} and E. Getz and Robert Fulton and Fulton, {Lucinda L.} and McLellan, {Michael D.} and Wilson, {Richard K.} and Kai Ye and Fronick, {Catrina C.} and Maher, {Christopher A.} and Miller, {Christopher A.} and Wendl, {Michael C.} and Christopher Cabanski and Elaine Mardis and David Wheeler and Miruna Balasundaram and Butterfield, {Yaron S N} and Rebecca Carlsen and Eric Chuah and Noreen Dhalla and Ranabir Guin and Carrie Hirst and Darlene Lee and Li, {Haiyan I.} and Michael Mayo and Moore, {Richard A.} and Mungall, {Andrew J.} and Schein, {Jacqueline E.} and Payal Sipahimalani and Angela Tam and Richard Varhol and Robertson, {A. Gordon} and Natasja Wye and Nina Thiessen and Holt, {Robert A.} and Jones, {Steven J M} and Marra, {Marco A.} and Marcin Imielinski and Onofrio, {Robert C.} and Eran Hodis and Travis Zack and Elena Helman and Pedamallu, {Chandra Sekhar} and Jill Mesirov and Gordon Saksena and Schumacher, {Steven E.} and Carter, {Scott L.} and Levi Garraway and Rameen Beroukhim and Semin Lee and Mahadeshwar, {Harshad S.} and Angeliki Pantazi and Alexei Protopopov and Xiaojia Ren and Sahil Seth and Xingzhi Song and Jiabin Tang and Lixing Yang and Jianhua Zhang and Chen, {Peng Chieh} and Michael Parfenov and Xu, {Andrew Wei} and Netty Santoso and Lynda Chin and Park, {Peter J.} and Hoadley, {Katherine A.} and Auman, {J. Todd} and Shaowu Meng and Yan Shi and Elizabeth Buda and Scot Waring and Umadevi Veluvolu and Donghui Tan and Mieczkowski, {Piotr A.} and Jones, {Corbin D.} and Simons, {Janae V.} and Soloway, {Matthew G.} and Tom Bodenheimer and Jefferys, {Stuart R.} and Jeffrey Roach and Hoyle, {Alan P.} and Junyuan Wu and Saianand Balu and Darshan Singh and Prins, {Jan F.} and Marron, {J. S.} and Parker, {Joel S.} and Perou, {Charles M.} and Jinze Liu and Maglinte, {Dennis T.} and Lai, {Philip H.} and Bootwalla, {Moiz S.} and {Van Den Berg}, {David J.} and Timothy Triche and Juok Cho and Daniel DiCara and David Heiman and Pei Lin and William Mallard and Douglas Voet and Hailei Zhang and Lihua Zou and Noble, {Michael S.} and Nils Gehlenborg and Helga Thorvaldsdottir and Nazaire, {Marc Danie} and Jim Robinson and Aksoy, {B. Arman} and Giovanni Ciriello and Taylor, {Barry S.} and Gideon Dresdner and Jianjiong Gao and Benjamin Gross and Seshan, {Venkatraman E.} and Boris Reva and Sumer, {S. Onur} and Nils Weinhold and Chris Sander and Sam Ng and Jingchun Zhu and Benz, {Christopher C.} and Christina Yau and David Haussler and Spellman, {Paul T.} and Kimes, {Patrick K.} and Broom, {Bradley M.} and Jing Wang and Yiling Lu and Ng, {Patrick Kwok Shing} and Lixia Diao and Wenbin Liu and Amos, {Christopher I.} and Rehan Akbani and Mills, {Gordon B.} and Erin Curley and Joseph Paulauskis and Kevin Lau and Scott Morris and Troy Shelton and David Mallery and Johanna Gardner and Robert Penny and Charles Saller and Katherine Tarvin and Richards, {William G.} and Robert Cerfolio and Ayesha Bryant and Raymond, {Daniel P.} and Pennell, {Nathan A.} and Carol Farver and Christine Czerwinski and Lori Huelsenbeck-Dill and Mary Iacocca and Nicholas Petrelli and Brenda Rabeno and Jennifer Brown and Thomas Bauer and Dolzhanskiy, {Cureline Oleg} and Olga Potapova and Daniil Rotin and Olga Voronina and Elena Nemirovich-Danchenko and Fedosenko, {Konstantin V.} and Anthony Gal and Madhusmita Behera and Ramalingam, {Suresh S.} and Gabriel Sica and Douglas Flieder and Jeff Boyd and Weaver, {Jo Ellen} and Bernard Kohl and Thinh, {Dang Huy Quoc} and George Sandusky and Hartmut Juhl and Edwina Duhig and Peter Illei and Edward Gabrielson and James Shin and Beverly Lee and Kristen Rogers and Dante Trusty and Brock, {Malcolm V.} and Christina Williamson and Eric Burks and Kimberly Rieger-Christ and Antonia Holway and Travis Sullivan and Asiedu, {Michael K.} and Farhad Kosari and Natasha Rekhtman and Maureen Zakowski and Rusch, {Valerie W.} and Paul Zippile and James Suh and Harvey Pass and Chandra Goparaju and Yvonne Owusu-Sarpong and Bartlett, {John M S} and Sugy Kodeeswaran and Jeremy Parfitt and Harmanjatinder Sekhon and Monique Albert and John Eckman and Myers, {Jerome B.} and Carl Morrison and Carmelo Gaudioso and Borgia, {Jeffrey A.} and Philip Bonomi and Mark Pool and Liptay, {Michael J.} and Fedor Moiseenko and Irina Zaytseva and Hendrik Dienemann and Michael Meister and Schnabel, {Philipp A.} and Muley, {Thomas R.} and Martin Peifer and Carmen Gomez-Fernandez and Lynn Herbert and Sophie Egea and Mei Huang and Thorne, {Leigh B.} and Lori Boice and Salazar, {Ashley Hill} and Funkhouser, {William K.} and Rathmell, {W. Kimryn} and Rajiv Dhir and Yousem, {Samuel A.} and Sanja Dacic and Frank Schneider and Siegfried, {Jill M.} and Richard Hajek and Watson, {Mark A.} and Sandra McDonald and Bryan Meyers and Belinda Clarke and Yang, {Ian A.} and Fong, {Kwun M.} and Lindy Hunter and Morgan Windsor and Bowman, {Rayleen V.} and Solange Peters and Igor Letovanec and Khan, {Khurram Z.} and Jensen, {Mark A.} and Snyder, {Eric E.} and Deepak Srinivasan and Kahn, {Ari B.} and Julien Baboud and Pot, {David A.} and Shaw, {Kenna R Mills} and Margi Sheth and Tanja Davidsen and Demchok, {John A.} and Liming Yang and Zhining Wang and Roy Tarnuzzer and Zenklusen, {Jean Claude} and Ozenberger, {Bradley A.} and Sofia, {Heidi J.} and Richard Cheney",
year = "2014",
doi = "10.1038/nature13385",
language = "English",
volume = "511",
pages = "543--550",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7511",

}

TY - JOUR

T1 - Comprehensive molecular profiling of lung adenocarcinoma

T2 - The cancer genome atlas research network

AU - Collisson, Eric A.

AU - Campbell, Joshua D.

AU - Brooks, Angela N.

AU - Berger, Alice H.

AU - Lee, William

AU - Chmielecki, Juliann

AU - Beer, David G.

AU - Cope, Leslie

AU - Creighton, Chad J.

AU - Danilova, Ludmila

AU - Ding, Li

AU - Getz, Gad

AU - Hammerman, Peter S.

AU - Hayes, D. Neil

AU - Hernandez, Bryan

AU - Herman, James G.

AU - Heymach, John V.

AU - Jurisica, Igor

AU - Kucherlapati, Raju

AU - Kwiatkowski, David

AU - Ladanyi, Marc

AU - Robertson, Gordon

AU - Schultz, Nikolaus

AU - Shen, Ronglai

AU - Sinha, Rileen

AU - Sougnez, Carrie

AU - Tsao, Ming Sound

AU - Travis, William D.

AU - Weinstein, John N.

AU - Wigle, Dennis A.

AU - Wilkerson, Matthew D.

AU - Chu, Andy

AU - Cherniack, Andrew D.

AU - Hadjipanayis, Angela

AU - Rosenberg, Mara

AU - Weisenberger, Daniel J.

AU - Laird, Peter W.

AU - Radenbaugh, Amie

AU - Ma, Singer

AU - Stuart, Joshua M.

AU - Byers, Lauren Averett

AU - Baylin, Stephen B.

AU - Govindan, Ramaswamy

AU - Meyerson, Matthew

AU - Gabriel, Stacey B.

AU - Cibulskis, Kristian

AU - Kim, Jaegil

AU - Stewart, Chip

AU - Lichtenstein, Lee

AU - Lander, Eric S.

AU - Lawrence, Michael S.

AU - Getz, E.

AU - Fulton, Robert

AU - Fulton, Lucinda L.

AU - McLellan, Michael D.

AU - Wilson, Richard K.

AU - Ye, Kai

AU - Fronick, Catrina C.

AU - Maher, Christopher A.

AU - Miller, Christopher A.

AU - Wendl, Michael C.

AU - Cabanski, Christopher

AU - Mardis, Elaine

AU - Wheeler, David

AU - Balasundaram, Miruna

AU - Butterfield, Yaron S N

AU - Carlsen, Rebecca

AU - Chuah, Eric

AU - Dhalla, Noreen

AU - Guin, Ranabir

AU - Hirst, Carrie

AU - Lee, Darlene

AU - Li, Haiyan I.

AU - Mayo, Michael

AU - Moore, Richard A.

AU - Mungall, Andrew J.

AU - Schein, Jacqueline E.

AU - Sipahimalani, Payal

AU - Tam, Angela

AU - Varhol, Richard

AU - Robertson, A. Gordon

AU - Wye, Natasja

AU - Thiessen, Nina

AU - Holt, Robert A.

AU - Jones, Steven J M

AU - Marra, Marco A.

AU - Imielinski, Marcin

AU - Onofrio, Robert C.

AU - Hodis, Eran

AU - Zack, Travis

AU - Helman, Elena

AU - Pedamallu, Chandra Sekhar

AU - Mesirov, Jill

AU - Saksena, Gordon

AU - Schumacher, Steven E.

AU - Carter, Scott L.

AU - Garraway, Levi

AU - Beroukhim, Rameen

AU - Lee, Semin

AU - Mahadeshwar, Harshad S.

AU - Pantazi, Angeliki

AU - Protopopov, Alexei

AU - Ren, Xiaojia

AU - Seth, Sahil

AU - Song, Xingzhi

AU - Tang, Jiabin

AU - Yang, Lixing

AU - Zhang, Jianhua

AU - Chen, Peng Chieh

AU - Parfenov, Michael

AU - Xu, Andrew Wei

AU - Santoso, Netty

AU - Chin, Lynda

AU - Park, Peter J.

AU - Hoadley, Katherine A.

AU - Auman, J. Todd

AU - Meng, Shaowu

AU - Shi, Yan

AU - Buda, Elizabeth

AU - Waring, Scot

AU - Veluvolu, Umadevi

AU - Tan, Donghui

AU - Mieczkowski, Piotr A.

AU - Jones, Corbin D.

AU - Simons, Janae V.

AU - Soloway, Matthew G.

AU - Bodenheimer, Tom

AU - Jefferys, Stuart R.

AU - Roach, Jeffrey

AU - Hoyle, Alan P.

AU - Wu, Junyuan

AU - Balu, Saianand

AU - Singh, Darshan

AU - Prins, Jan F.

AU - Marron, J. S.

AU - Parker, Joel S.

AU - Perou, Charles M.

AU - Liu, Jinze

AU - Maglinte, Dennis T.

AU - Lai, Philip H.

AU - Bootwalla, Moiz S.

AU - Van Den Berg, David J.

AU - Triche, Timothy

AU - Cho, Juok

AU - DiCara, Daniel

AU - Heiman, David

AU - Lin, Pei

AU - Mallard, William

AU - Voet, Douglas

AU - Zhang, Hailei

AU - Zou, Lihua

AU - Noble, Michael S.

AU - Gehlenborg, Nils

AU - Thorvaldsdottir, Helga

AU - Nazaire, Marc Danie

AU - Robinson, Jim

AU - Aksoy, B. Arman

AU - Ciriello, Giovanni

AU - Taylor, Barry S.

AU - Dresdner, Gideon

AU - Gao, Jianjiong

AU - Gross, Benjamin

AU - Seshan, Venkatraman E.

AU - Reva, Boris

AU - Sumer, S. Onur

AU - Weinhold, Nils

AU - Sander, Chris

AU - Ng, Sam

AU - Zhu, Jingchun

AU - Benz, Christopher C.

AU - Yau, Christina

AU - Haussler, David

AU - Spellman, Paul T.

AU - Kimes, Patrick K.

AU - Broom, Bradley M.

AU - Wang, Jing

AU - Lu, Yiling

AU - Ng, Patrick Kwok Shing

AU - Diao, Lixia

AU - Liu, Wenbin

AU - Amos, Christopher I.

AU - Akbani, Rehan

AU - Mills, Gordon B.

AU - Curley, Erin

AU - Paulauskis, Joseph

AU - Lau, Kevin

AU - Morris, Scott

AU - Shelton, Troy

AU - Mallery, David

AU - Gardner, Johanna

AU - Penny, Robert

AU - Saller, Charles

AU - Tarvin, Katherine

AU - Richards, William G.

AU - Cerfolio, Robert

AU - Bryant, Ayesha

AU - Raymond, Daniel P.

AU - Pennell, Nathan A.

AU - Farver, Carol

AU - Czerwinski, Christine

AU - Huelsenbeck-Dill, Lori

AU - Iacocca, Mary

AU - Petrelli, Nicholas

AU - Rabeno, Brenda

AU - Brown, Jennifer

AU - Bauer, Thomas

AU - Dolzhanskiy, Cureline Oleg

AU - Potapova, Olga

AU - Rotin, Daniil

AU - Voronina, Olga

AU - Nemirovich-Danchenko, Elena

AU - Fedosenko, Konstantin V.

AU - Gal, Anthony

AU - Behera, Madhusmita

AU - Ramalingam, Suresh S.

AU - Sica, Gabriel

AU - Flieder, Douglas

AU - Boyd, Jeff

AU - Weaver, Jo Ellen

AU - Kohl, Bernard

AU - Thinh, Dang Huy Quoc

AU - Sandusky, George

AU - Juhl, Hartmut

AU - Duhig, Edwina

AU - Illei, Peter

AU - Gabrielson, Edward

AU - Shin, James

AU - Lee, Beverly

AU - Rogers, Kristen

AU - Trusty, Dante

AU - Brock, Malcolm V.

AU - Williamson, Christina

AU - Burks, Eric

AU - Rieger-Christ, Kimberly

AU - Holway, Antonia

AU - Sullivan, Travis

AU - Asiedu, Michael K.

AU - Kosari, Farhad

AU - Rekhtman, Natasha

AU - Zakowski, Maureen

AU - Rusch, Valerie W.

AU - Zippile, Paul

AU - Suh, James

AU - Pass, Harvey

AU - Goparaju, Chandra

AU - Owusu-Sarpong, Yvonne

AU - Bartlett, John M S

AU - Kodeeswaran, Sugy

AU - Parfitt, Jeremy

AU - Sekhon, Harmanjatinder

AU - Albert, Monique

AU - Eckman, John

AU - Myers, Jerome B.

AU - Morrison, Carl

AU - Gaudioso, Carmelo

AU - Borgia, Jeffrey A.

AU - Bonomi, Philip

AU - Pool, Mark

AU - Liptay, Michael J.

AU - Moiseenko, Fedor

AU - Zaytseva, Irina

AU - Dienemann, Hendrik

AU - Meister, Michael

AU - Schnabel, Philipp A.

AU - Muley, Thomas R.

AU - Peifer, Martin

AU - Gomez-Fernandez, Carmen

AU - Herbert, Lynn

AU - Egea, Sophie

AU - Huang, Mei

AU - Thorne, Leigh B.

AU - Boice, Lori

AU - Salazar, Ashley Hill

AU - Funkhouser, William K.

AU - Rathmell, W. Kimryn

AU - Dhir, Rajiv

AU - Yousem, Samuel A.

AU - Dacic, Sanja

AU - Schneider, Frank

AU - Siegfried, Jill M.

AU - Hajek, Richard

AU - Watson, Mark A.

AU - McDonald, Sandra

AU - Meyers, Bryan

AU - Clarke, Belinda

AU - Yang, Ian A.

AU - Fong, Kwun M.

AU - Hunter, Lindy

AU - Windsor, Morgan

AU - Bowman, Rayleen V.

AU - Peters, Solange

AU - Letovanec, Igor

AU - Khan, Khurram Z.

AU - Jensen, Mark A.

AU - Snyder, Eric E.

AU - Srinivasan, Deepak

AU - Kahn, Ari B.

AU - Baboud, Julien

AU - Pot, David A.

AU - Shaw, Kenna R Mills

AU - Sheth, Margi

AU - Davidsen, Tanja

AU - Demchok, John A.

AU - Yang, Liming

AU - Wang, Zhining

AU - Tarnuzzer, Roy

AU - Zenklusen, Jean Claude

AU - Ozenberger, Bradley A.

AU - Sofia, Heidi J.

AU - Cheney, Richard

PY - 2014

Y1 - 2014

N2 - Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

AB - Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84905029258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905029258&partnerID=8YFLogxK

U2 - 10.1038/nature13385

DO - 10.1038/nature13385

M3 - Article

VL - 511

SP - 543

EP - 550

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7511

ER -