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Nature DOI:10.1038/nature11404

Comprehensive genomic characterization of squamous cell lung cancers.

Publication TypeJournal Article
Year of Publication2012
AuthorsThe Cancer Genome Atlas Research, N, institution.) (Participants are arranged by area of contribution and then by, , Genome sequencing centres: Broad, I, Hammerman, PS, Lawrence, MS, Voet, D, Jing, R, Cibulskis, K, Sivachenko, A, Stojanov, P, McKenna, A, Lander, ES, Gabriel, S, Getz, G, Sougnez, C, Imielinski, M, Helman, E, Hernandez, B, Pho, NH, Meyerson, M, Chu, A, Chun, HJ, Mungall, AJ, Pleasance, E, Gordon Robertson, A, Sipahimalani, P, Stoll, D, Balasundaram, M, Birol, I, Butterfield, YS, Chuah, E, Coope, RJ, Dhalla, N, Guin, R, He, A, Hirst, C, Hirst, M, Holt, RA, Lee, D, Li, HI, Mayo, M, Moore, RA, Schein, JE, Slobodan, JR, Tam, A, Thiessen, N, Zhao, Y, Jones, SJ, Marra, MA, Broad, I, Saksena, G, Cherniack, AD, Schumacher, SE, Tabak, B, Carter, SL, Pho, NH, Nguyen, H, Onofrio, RC, Crenshaw, A, Ardlie, K, Beroukhim, R, Winckler, W, Hammerman, PS, Getz, G, Meyerson, M, Protopopov, A, Zhang, J, Hadjipanayis, A, Lee, S, Xi, R, Yang, L, Ren, X, Zhang, H, Chin, L, Park, PJ, Kucherlapati, R, Socci, ND, Liang, Y, Schultz, N, Viale, A, Sander, C, Ladanyi, M, University of North Carolina at Chapel, H, Todd Auman, J, 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, Wu, J, Bodenheimer, T, Hoyle, AP, Simons, JV, Soloway, MG, Mose, LE, Jefferys, SR, Balu, S, Liu, J, Chiang, DY, Neil Hayes, D, Perou, CM, Cope, L, Weisenberger, DJ, Maglinte, DT, Van Den Berg, DJ, Triche Jr, T, Baylin, SB, Laird, PW, Genome data analysis centres: Broad, I, Getz, G, Noble, M, Voet, D, Saksena, G, Gehlenborg, N, Dicara, D, Zhang, J, Zhang, H, Wu, CJ, Lawrence, MS, Zou, L, Sivachenko, A, Lin, P, Stojanov, P, Jing, R, Cho, J, Nazaire, MD, Robinson, J, Mesirov, J, Park, PJ, Chin, L, Memorial Sloan-Kettering Cancer, C, Schultz, N, Sinha, R, Ciriello, G, Cerami, E, Gross, B, Jacobsen, A, Gao, J, Arman Aksoy, B, Weinhold, N, Taylor, BS, Antipin, Y, Reva, B, Shen, R, Ladanyi, M, Sander, C, The University of Texas MD Anderson Cancer, C, Akbani, R, Zhang, N, Broom, BM, Wakefield, C, Weinstein, JN, Haussler, D, Benz, CC, Stuart, JM, Zhu, J, Szeto, C, Yau, C, Ng, S, Goldstein, T, Waltman, P, Ellrott, K, University of North Carolina at Chapel, H, Wilkerson, MD, Todd Auman, J, Hoadley, KA, Wu, J, Bodenheimer, T, Hoyle, AP, Simons, JV, Soloway, MG, Mose, LE, Jefferys, SR, Balu, S, Liu, Y, Wang, K, Liu, J, Neil Hayes, D, Perou, CM, Creighton, CJ, Zhang, Y, Travis, WD, Myers, J, Tsao, MS, Penny, R, Mallery, D, Shelton, T, Hatfield, M, Morris, S, Shelton, C, Sherman, M, Paulauskis, J, Meyerson, M, Baylin, SB, Akbani, R, Chiang, D, Chu, A, Chun, E, Cope, L, Creighton, CJ, Ding, L, Getz, G, Hammerman, PS, Neil Hayes, D, Hernandez, B, Imielinski, M, Jurisica, I, Kucherlapati, R, Kwiatkowski, D, Ladanyi, M, Lawrence, MS, Ng, S, Pao, W, Penny, R, Rusch, V, Sander, C, Schultz, N, Shen, R, Sinha, R, Sivachenko, A, Sougnez, C, Stoll, D, Stuart, J, Thomas, RK, Tsao, MS, Travis, WD, Weinstein, JN, Wilkerson, MD, centre Data coordination, , 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, Srinivasan, D, Raman, R, Girshik, S, Alonso, S, Pot, DA, Tsao, MS, Boyd, J, Weaver, J, Lee, B, Dhir, R, Potapova, O, Nemirovich-Danchenko, E, Rusch, V, Iacocca, MV, Brown, J, Rabeno, B, Czerwinski, C, Petrelli, N, Eckman, J, Myers, J, Kimryn Rathmell, W, Huang, M, Boice, L, Hill, A, Penny, R, Mallery, D, Curley, E, Shelton, C, Morrison, C, Gaudioso, C, Bartlett, JM, Kodeeswaran, S, Project team: National Cancer, I, Mills Shaw, KR, Sheth, M, Yang, L, Davidsen, T, Demchok, JA, Eley, G, National Human Genome Research, I, Guyer, MS, Ozenberger, BA, Peterson, J, Sofia, HJ, committee Writing, , Hammerman, PS, Neil Hayes, D, Wilkerson, MD, Schultz, N, Chu, A, Cope, L, Creighton, CJ, Getz, G, Johnson, BE, Kucherlapati, R, Ladanyi, M, Sander, C, Shen, R, Sinha, R, Sivachenko, A, Thomas, RK, Travis, WD, Tsao, MS, Weinstein, JN, Baylin, SB, Meyerson, M
JournalNature
Date Published2012/09/09
ISSN0028-0836
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.

URLhttp://dx.doi.org/10.1038/nature11404
DOI10.1038/nature11404
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22960745?dopt=Abstract