Comprehensive genomic characterization defines human glioblastoma genes and core pathways.
McLendon, Roger 1; Friedman, Allan 2; Bigner, Darrell 1; Van Meir, Erwin G. 3,4,5; Brat, Daniel J. 5,6; Mastrogianakis, Gena M. 3; Olson, Jeffrey J. 3,4,5; Mikkelsen, Tom 7; Lehman, Norman 8; Aldape, Ken 9; Alfred Yung, W. K. 10; Bogler, Oliver 11; Weinstein, John N. 57; VandenBerg, Scott 12; Berger, Mitchel 13; Prados, Michael 13; Muzny, Donna 14; Morgan, Margaret 14; Scherer, Steve 14; Sabo, Aniko 14; Nazareth, Lynn 14; Lewis, Lora 14; Hall, Otis 14; Zhu, Yiming 14; Ren, Yanru 14; Alvi, Omar 14; Yao, Jiqiang 14; Hawes, Alicia 14; Jhangiani, Shalini 14; Fowler, Gerald 14; SanLucas, Anthony 14; Kovar, Christie 14; Cree, Andrew 14; Dinh, Huyen 14; Santibanez, Jireh 14; Joshi, Vandita 14; Gonzalez-Garay, Manuel L. 14; Miller, Christopher A. 14,15; Milosavljevic, Aleksandar 14,15,16; Donehower, Larry 17; Wheeler, David A. 14; Gibbs, Richard A. 14; Cibulskis, Kristian 18; Sougnez, Carrie 18; Fennell, Tim 18; Mahan, Scott 18; Wilkinson, Jane 18; Ziaugra, Liuda 18; Onofrio, Robert 18; Bloom, Toby 18; Nicol, Rob 18; Ardlie, Kristin 18; Baldwin, Jennifer 18; Gabriel, Stacey 18; Lander, Eric S. 18,19,20; Ding, Li 21; Fulton, Robert S. 21; McLellan, Michael D. 21; Wallis, John 21; Larson, David E. 21; Shi, Xiaoqi 21; Abbott, Rachel 21; Fulton, Lucinda 21; Chen, Ken 21; Koboldt, Daniel C. 21; Wendl, Michael C. 21; Meyer, Rick 21; Tang, Yuzhu 21; Lin, Ling 21; Osborne, John R. 21; Dunford-Shore, Brian H. 21; Miner, Tracie L. 21; Delehaunty, Kim 21; Markovic, Chris 21; Swift, Gary 21; Courtney, William 21; Pohl, Craig 21; Abbott, Scott 21; Hawkins, Amy 21; Leong, Shin 21; Haipek, Carrie 21; Schmidt, Heather 21; Wiechert, Maddy 21; Vickery, Tammi 21; Scott, Sacha 21; Dooling, David J. 21; Chinwalla, Asif 21; Weinstock, George M. 21; Mardis, Elaine R. 21; Wilson, Richard K. 21; Getz, Gad 18; Winckler, Wendy 18,22,33; Verhaak, Roel G. W. 18,22,33; Lawrence, Michael S. 18; O'Kelly, Michael 18; Robinson, Jim 18; Alexe, Gabriele 18; Beroukhim, Rameen 18,22,23; Carter, Scott 18; Chiang, Derek 18,22; Gould, Josh 18; Gupta, Supriya 18; Korn, Josh 18; Mermel, Craig 18,22; Mesirov, Jill 18; Monti, Stefano 18; Nguyen, Huy 18; Parkin, Melissa 18; Reich, Michael 18; Stransky, Nicolas 18; Weir, Barbara A. 18,22,23; Garraway, Levi 18,22,23; Golub, Todd 18,22,23; Meyerson, Matthew 18,22,23; Chin, Lynda 22,24,25; Protopopov, Alexei 24; Zhang, Jianhua 24; Perna, Ilana 24; Aronson, Sandy 26; Sathiamoorthy, Narayanan 26; Ren, Georgia 24; Yao, Jun 24; Wiedemeyer, W. Ruprecht 22; Kim, Hyunsoo 26; Won Kong, Sek 27,28; Xiao, Yonghong 24; Kohane, Isaac S. 26,27,29; Seidman, Jon 30; Park, Peter J. 26,27,29; Kucherlapati, Raju 26; Laird, Peter W. 31; Cope, Leslie 32; Herman, James G. 33; Weisenberger, Daniel J. 31; Pan, Fei 31; Van Den Berg, David 31; Neste, Van 34; Mi Yi, Joo 33; Schuebel, Kornel E. 33; Baylin, Stephen B. 33; Absher, Devin M. 35; Li, Jun Z. 36; Southwick, Audrey 37; Brady, Shannon 37; Aggarwal, Amita 37; Chung, Tisha 37; Sherlock, Gavin 37; Brooks, James D. 38; Myers, Richard M. 35; Spellman, Paul T. 39; Purdom, Elizabeth 40; Jakkula, Lakshmi R. 39; Lapuk, Anna V. 39; Marr, Henry 39; Dorton, Shannon 39; Gi Choi, Yoon 41; Han, Ju 39; Ray, Amrita 39; Wang, Victoria 40; Durinck, Steffen 39; Robinson, Mark 42; Wang, Nicholas J. 39; Vranizan, Karen 41; Peng, Vivian 41; Van Name, Eric 41; Fontenay, Gerald V. 39; Ngai, John 41; Conboy, John G. 39; Parvin, Bahram 39; Feiler, Heidi S. 39; Speed, Terence P. 40,42; Gray, Joe W. 39; Brennan, Cameron 43; Socci, Nicholas D. 44; Olshen, Adam 45; Taylor, Barry S. 44,46; Lash, Alex 44; Schultz, Nikolaus 44; Reva, Boris 44; Antipin, Yevgeniy 44; Stukalov, Alexey 44; Gross, Benjamin 44; Cerami, Ethan 44; Qing Wang, Wei 44; Qin, Li-Xuan 45; Seshan, Venkatraman E. 45; Villafania, Liliana 47; Cavatore, Magali 47; Borsu, Laetitia 48; Viale, Agnes 47; Gerald, William 48; Sander, Chris 44; Ladanyi, Marc 48; Perou, Charles M. 49,50; Hayes, D. Neil 51; Topal, Michael D. 50,52; Hoadley, Katherine A. 49; Qi, Yuan 51; Balu, Sai 52; Shi, Yan 52; Wu, Junyuan 52; Penny, Robert 53; Bittner, Michael 54; Shelton, Troy 53; Lenkiewicz, Elizabeth 53; Morris, Scott 53; Beasley, Debbie 53; Sanders, Sheri 53; Kahn, Ari 55; Sfeir, Robert 55; Chen, Jessica 55; Nassau, David 55; Feng, Larry 55; Hickey, Erin 55; Barker, Anna 58; Gerhard, Daniela S. 58; Vockley, Joseph 58; Compton, Carolyn 58; Vaught, Jim 58; Fielding, Peter 58; Ferguson, Martin L. 59; Schaefer, Carl 56; Zhang, Jinghui 56; Madhavan, Subhashree 56; Buetow, Kenneth H. 56; Collins, Francis 60; Good, Peter 60; Guyer, Mark 60; Ozenberger, Brad 60; Peterson, Jane 60; Thomson, Elizabeth 60
[Article]
Nature.
455(7216):1061-1068, October 23, 2008.
(Format: HTML, PDF)
Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas-the most common type of primary adult brain cancer-and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
(C) 2008 Nature Publishing Group