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Neil ORCID: 0000-0001-6203-7771, Perou, Charles M., Cope, Leslie, Danilova, Ludmila, Weisenberger, Daniel J., Maglinte, Dennis T., Pan, Fei, Van den Berg, David J., Triche, Timothy, Herman, James G., Baylin, Stephen B., Laird, Peter W., Getz, Gad, Noble, Michael, Voet, Doug, Saksena, Gordon, Gehlenborg, Nils ORCID: 0000-0003-0327-8297, DiCara, Daniel, Zhang, Jinhua, Zhang, Hailei, Wu, Chang-Jiun, Liu, Spring Yingchun, Lawrence, Michael S., Zou, Lihua, Sivachenko, Andrey, Lin, Pei, Stojanov, Petar, Jing, Rui, Cho, Juok, Nazaire, Marc-Danie, Robinson, Jim, Thorvaldsdottir, Helga, Mesirov, Jill, Park, Peter J., Chin, Lynda, Schultz, Nikolaus ORCID: 0000-0002-0131-4904, Sinha, Rileen ORCID: 0000-0001-5497-5055, Ciriello, Giovanni ORCID: 0000-0003-2021-8683, Cerami, Ethan, Gross, Benjamin, Jacobsen, Anders, Gao, Jianjiong, Aksoy, B. 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S., Liu, Yufeng, Wang, Kai, Liu, Jinze, Prins, Jan F., Hayes, D. Neil ORCID: 0000-0001-6203-7771, Perou, Charles M., Creighton, Chad J., Zhang, Yiqun, Travis, William D., Rekhtman, Natasha, Yi, Joanne, Aubry, Marie C., Cheney, Richard, Dacic, Sanja, Flieder, Douglas, Funkhouser, William, Illei, Peter, Myers, Jerome, Tsao, Ming-Sound, Penny, Robert, Mallery, David, Shelton, Troy, Hatfield, Martha, Morris, Scott, Yena, Peggy, Shelton, Candace, Sherman, Mark, Paulauskis, Joseph, Meyerson, Matthew ORCID: 0000-0002-9133-8108, Baylin, Stephen B., Govindan, Ramaswamy, Akbani, Rehan, Azodo, Ijeoma, Beer, David, Bose, Ron, Byers, Lauren A., Carbone, David, Chang, Li-Wei, Chiang, Derek, Chu, Andy, Chun, Elizabeth, Collisson, Eric, Cope, Leslie, Creighton, Chad J., Danilova, Ludmila, Ding, Li, Getz, Gad, Hammerman, Peter S., Hayes, D. Neil ORCID: 0000-0001-6203-7771, Hernandez, Bryan, Herman, James G., Heymach, John ORCID: 0000-0001-9068-8942, Ida, Cristiane, Imielinski, Marcin, Johnson, Bruce, Jurisica, Igor, Kaufman, Jacob, Kosari, Farhad, Kucherlapati, Raju, Kwiatkowski, David, Ladanyi, Marc, Lawrence, Michael S., Maher, Christopher A., Mungall, Andy, Ng, Sam, Pao, William, Peifer, Martin ORCID: 0000-0002-5243-5503, Penny, Robert, Robertson, Gordon, Rusch, Valerie ORCID: 0000-0003-2345-6900, Sander, Chris, Schultz, Nikolaus ORCID: 0000-0002-0131-4904, Shen, Ronglai, Siegfried, Jill, Sinha, Rileen ORCID: 0000-0001-5497-5055, Sivachenko, Andrey, Sougnez, Carrie, Stoll, Dominik, Stuart, Joshua ORCID: 0000-0002-2171-565X, Thomas, Roman K., Tomaszek, Sandra, Tsao, Ming-Sound, Travis, William D., Vaske, Charles ORCID: 0000-0001-8151-6612, Weinstein, John N., Weisenberger, Daniel ORCID: 0000-0001-8303-2603, Wheeler, David, Wigle, Dennis A., Wilkerson, Matthew D., Wilks, Christopher, Yang, Ping, Zhang, Jianjua John, Jensen, Mark A., Sfeir, Robert, Kahn, Ari B., Chu, Anna L., Kothiyal, Prachi, Wang, Zhining, Snyder, Eric E., Pontius, Joan, Pihl, Todd D., Ayala, Brenda, Backus, Mark, Walton, Jessica, Baboud, Julien, Berton, Dominique L., Nicholls, Matthew C., Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter A., Alonso, Shelley, Sanbhadti, Rashmi N., Barletta, Sean P., Greene, John M., Pot, David A., Tsao, Ming-Sound, Bandarchi-Chamkhaleh, Bizhan, Boyd, Jeff, Weaver, JoEllen, Wigle, Dennis A., Azodo, Ijeoma A., Tomaszek, Sandra C., Aubry, Marie Christine, Ida, Christiane M., Yang, Ping, Kosari, Farhad, Brock, Malcolm V., Rogers, Kristen, Rutledge, Marian, Brown, Travis, Lee, Beverly, Shin, James, Trusty, Dante, Dhir, Rajiv, Siegfried, Jill M., Potapova, Olga, Fedosenko, Konstantin V., Nemirovich-Danchenko, Elena, Rusch, Valerie ORCID: 0000-0003-2345-6900, Zakowski, Maureen, Iacocca, Mary V., Brown, Jennifer, Rabeno, Brenda, Czerwinski, Christine, Petrelli, Nicholas, Fan, Zhen, Todaro, Nicole, Eckman, John, Myers, Jerome, Rathmell, W. Kimryn, Thorne, Leigh B., Huang, Mei, Boice, Lori, Hill, Ashley, Penny, Robert, Mallery, David, Curley, Erin, Shelton, Candace, Yena, Peggy, Morrison, Carl, Gaudioso, Carmelo, Bartlett, Johnm. S., Kodeeswaran, Sugy, Zanke, Brent, Sekhon, Harman, David, Kerstin, Juhl, Hartmut, Van Le, Xuan, Kohl, Bernard, Thorp, Richard, Tien, Nguyen Viet, Van Bang, Nguyen, Sussman, Howard, Phu, Bui Duc, Hajek, Richard, PhiHung, Nguyen, Khan, Khurram Z., Muley, Thomas, Shaw, Kenna R. Mills, Sheth, Margi, Yang, Liming, Buetow, Ken, Davidsen, Tanja, Demchok, John A., Eley, Greg, Ferguson, Martin, Dillon, Laura A. L., Schaefer, Carl, Guyer, Mark S., Ozenberger, Bradley A., Palchik, Jacqueline D., Peterson, Jane, Sofia, Heidi J., Thomson, Elizabeth and Meyerson, Matthew ORCID: 0000-0002-9133-8108 (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489 (7417). S. 519 - 526. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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Abstract

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
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Cibulskis, KristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Gaudioso, CarmeloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartlett, Johnm. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Kohl, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thorp, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tien, Nguyen VietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Bang, NguyenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sussman, HowardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phu, Bui DucUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hajek, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
PhiHung, NguyenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, Khurram Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muley, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shaw, Kenna R. MillsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sheth, MargiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, LimingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buetow, KenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davidsen, TanjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demchok, John A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eley, GregUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferguson, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dillon, Laura A. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, CarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guyer, Mark S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozenberger, Bradley A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palchik, Jacqueline D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterson, JaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sofia, Heidi J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomson, ElizabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyerson, MatthewUNSPECIFIEDorcid.org/0000-0002-9133-8108UNSPECIFIED
URN: urn:nbn:de:hbz:38-482752
DOI: 10.1038/nature11404
Journal or Publication Title: Nature
Volume: 489
Number: 7417
Page Range: S. 519 - 526
Date: 2012
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COPY-NUMBER ALTERATION; THERAPEUTIC TARGET; MUTATIONS; GENE; AMPLIFICATION; CARCINOMA; SENSITIVITY; LANDSCAPE; GEFITINIB; ONCOGENEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48275

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