Comprehensive genomic characterization of squamous cell lung cancers.

Comprehensive genomic characterization of squamous cell lung cancers.
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DOI:
10.1038/nature11404
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发表时间:
2012-09-27
期刊:
影响因子:
64.8
通讯作者:
Meyerson, Matthew
Meyerson, Matthew
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hammerman, Peter S.;Lawrence, Michael S.;Voet, Douglas;Jing, Rui;Cibulskis, Kristian;Sivachenko, Andrey;Stojanov, Petar;McKenna, Aaron;Lander, Eric S.;Gabriel, Stacey;Getz, Gad;Sougnez, Carrie;Imielinski, Marcin;Helman, Elena;Hernandez, Bryan;Pho, Nam H.;Meyerson, Matthew;Chu, Andy;Chun, Hye-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;Hirst, Anhe 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.;Pho, Nam H.;Nguyen, Huy;Onofrio, Robert C.;Crenshaw, Andrew;Ardlie, Kristin;Beroukhim, Rameen;Winckler, Wendy;Hammerman, Peter S.;Getz, Gad;Meyerson, Matthew;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.;Mose, Lisle E.;Jefferys, Stuart R.;Balu, Saianand;O'Connor, Brian D.;Prins, Jan F.;Liu, Jinze;Chiang, Derek Y.;Hayes, D. Neil;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;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;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;Shen, Ronglai;Mo, Qianxing;Seshan, Venkatraman;Paik, Paul K.;Ladanyi, Marc;Sander, Chris;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;Ellrott, Kyle;Collisson, Eric A.;Zerbino, Daniel;Wilks, Christopher;Ma, Singer;Craft, Brian;Wilkerson, Matthew D.;Auman, J. Todd;Hoadley, Katherine A.;Du, Ying;Cabanski, Christopher;Walter, Vonn;Singh, Darshan;Wu, Junyuan;Gulabani, Anisha;Bodenheimer, Tom;Hoyle, Alan P.;Simons, Janae V.;Soloway, Matthew G.;Mose, Lisle E.;Jefferys, Stuart R.;Balu, Saianand;Marron, J. S.;Liu, Yufeng;Wang, Kai;Liu, Jinze;Prins, Jan F.;Hayes, D. Neil;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;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;Hernandez, Bryan;Herman, James G.;Heymach, John;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;Penny, Robert;Robertson, Gordon;Rusch, Valerie;Sander, Chris;Schultz, Nikolaus;Shen, Ronglai;Siegfried, Jill;Sinha, Rileen;Sivachenko, Andrey;Sougnez, Carrie;Stoll, Dominik;Stuart, Joshua;Thomas, Roman K.;Tomaszek, Sandra;Tsao, Ming-Sound;Travis, William D.;Vaske, Charles;Weinstein, John N.;Weisenberger, Daniel;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;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;Meyerson, Matthew

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肺鳞状细胞癌(Lung squamous cell carcinoma,lung SqCC)是一种常见的肺癌,每年在全世界造成约40万人死亡。肺SqCC的基因组改变尚未得到全面表征,也没有专门针对其治疗开发分子靶向药物。作为癌症基因组图谱(TCGA)的一部分,我们分析了178个肺SqCC,以提供基因组和表观基因组改变的全面景观。肺SqCC的特征在于复杂的基因组改变,每个肿瘤平均有360个外显子突变,165个基因组重排和323个拷贝数改变片段。我们在几乎所有的标本中发现了18个基因的统计学重复突变,包括TP 53突变。在HLA-A I类主要组织相容性基因中发现了以前未报道的功能丧失突变。显著改变的途径包括34%的NFE 2L 2/KEAP 1,44%的鳞状分化基因,47%的PI 3 K/AKT和72%的CDKN 2A/RB 1。我们在大多数肿瘤中确定了一个潜在的治疗靶点,为肺SqCC治疗提供了新的研究途径。
Lung squamous cell carcinoma (lung SqCC) is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in lung SqCC have not been comprehensively characterized and no molecularly targeted agents have been developed specifically for its treatment. As part of The Cancer Genome Atlas (TCGA), we profiled 178 lung SqCCs to provide a comprehensive landscape of genomic and epigenomic alterations. Lung SqCC is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumor. We found statistically recurrent mutations in 18 genes in including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations were seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2/KEAP1 in 34%, squamous differentiation genes in 44%, PI3K/AKT in 47%, and CDKN2A/RB1 in 72% of tumors. We identified a potential therapeutic target in the majority of tumors, offering new avenues of investigation for lung SqCC treatment.
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