Comprehensive molecular characterization of human colon and rectal cancer.
Genome Sequencing Center Baylor College of Medicine; Muzny, Donna M. 1; Bainbridge, Matthew N. 1; Chang, Kyle 1; Dinh, Huyen H. 1; Drummond, Jennifer A. 1; Fowler, Gerald 1; Kovar, Christie L. 1; Lewis, Lora R. 1; Morgan, Margaret B. 1; Newsham, Irene F. 1; Reid, Jeffrey G. 1; Santibanez, Jireh 1; Shinbrot, Eve 1; Trevino, Lisa R. 1; Wu, Yuan-Qing 1; Wang, Min 1; Gunaratne, Preethi 1,2; Donehower, Lawrence A. 1,3; Creighton, Chad J. 1,3; Wheeler, David A. 1; Gibbs, Richard A. 1; Genome Sequencing Center Broad Institute; Lawrence, Michael S. 4; Voet, Douglas 4; Jing, Rui 4; Cibulskis, Kristian 5; Sivachenko, Andrey 3,4; Stojanov, Petar 4; McKenna, Aaron 4; Lander, Eric S. 4,6,7; Gabriel, Stacey 8; Getz, Gad 4; Genome Sequencing Center Washington University in St Louis; Ding, Li 9,10; Fulton, Robert S. 9; Koboldt, Daniel C. 9; Wylie, Todd 9; Walker, Jason 9; Dooling, David J. 9,10; Fulton, Lucinda 9; Delehaunty, Kim D. 9; Fronick, Catrina C. 9; Demeter, Ryan 9; Mardis, Elaine R. 9,10,11; Wilson, Richard K. 9,10,11; Genome Characterization Center BC Cancer Agency; Chu, Andy 12; Chun, Hye-Jung E. 12; Mungall, Andrew J. 12; Pleasance, Erin 12; Robertson, Gordon A. 12; Stoll, Dominik 12; Balasundaram, Miruna 12; Birol, Inanc 12; Butterfield, Yaron S. N. 12; Chuah, Eric 12; Coope, Robin J. N. 12; Dhalla, Noreen 12; Guin, Ranabir 12; Hirst, Carrie 12; Hirst, Martin 12; Holt, Robert A. 12; Lee, Darlene 12; Li, Haiyan I. 12; Mayo, Michael 12; Moore, Richard A. 12; Schein, Jacqueline E. 12; Slobodan, Jared R. 12; Tam, Angela 12; Thiessen, Nina 12; Varhol, Richard 12; Zeng, Thomas 12; Zhao, Yongjun 12; Jones, Steven J. M. 12; Marra, Marco A. 12; Genome-Characterization Center Broad Institute; Bass, Adam J. 4,13; Ramos, Alex H. 4,13; Saksena, Gordon 4; Cherniack, Andrew D. 4; Schumacher, Stephen E. 4,13; Tabak, Barbara 4,13; Carter, Scott L. 4,13; Pho, Nam H. 4; Nguyen, Huy 4; Onofrio, Robert C. 4; Crenshaw, Andrew 4; Ardlie, Kristin 4; Beroukhim, Rameen 4,13; Winckler, Wendy 4; Meyerson, Matthew 4,13,14; Genome-Characterization Center Brigham and Women's Hospital and Harvard Medical School; Protopopov, Alexei 15; Zhang, Juinhua 4,15; Hadjipanayis, Angela 16,17; Lee, Eunjung 17,18; Xi, Ruibin 18; Yang, Lixing 18; Ren, Xiaojia 15; Zhang, Hailei 4,15; Sathiamoorthy, Narayanan 19; Shukla, Sachet 4,15; Chen, Peng-Chieh 16,17; Haseley, Psalm 17,18; Xiao, Yonghong 15; Lee, Semin 18; Seidman, Jonathan 16; Chin, Lynda 4,15,20; Park, Peter J. 17,18,19; Kucherlapati, Raju 16,17; Genome-Characterization Center University of North Carolina, Chapel Hill; Auman, Todd J. 21,22; Hoadley, Katherine A. 23,24,25; Du, Ying 25; Wilkerson, Matthew D. 25; Shi, Yan 25; Liquori, Christina 25; Meng, Shaowu 25; Li, Ling 25; Turman, Yidi J. 25; Topal, Michael D. 24,25; Tan, Donghui 26; Waring, Scot 25; Buda, Elizabeth 25; Walsh, Jesse 25; Jones, Corbin D. 27; Mieczkowski, Piotr A. 23; Singh, Darshan 28; Wu, Junyuan 25; Gulabani, Anisha 25; Dolina, Peter 25; Bodenheimer, Tom 25; Hoyle, Alan P. 25; Simons, Janae V. 25; Soloway, Matthew 25; Mose, Lisle E. 24; Jefferys, Stuart R. 24; Balu, Saianand 25; O'Connor, Brian D. 25; Prins, Jan F. 28; Chiang, Derek Y. 23,25; Hayes, Neil D. 25,29; Perou, Charles M. 23,24,25; Genome-Characterization Centers University of Southern California and Johns Hopkins University; Hinoue, Toshinori 30; Weisenberger, Daniel J. 30; Maglinte, Dennis T. 30; Pan, Fei 30; Berman, Benjamin P. 30; Van Den Berg, David J. 30; Shen, Hui 30; Triche, Timothy Jr 30; Baylin, Stephen B. 31; Laird, Peter W. 30; Genome Data Analysis Center Broad Institute; Noble, Michael 4; Voet, Doug 4; Gehlenborg, Nils 4,18; DiCara, Daniel 4; Wu, Chang-Jiun 4,15; Yingchun Liu, Spring 4,15; Zhou, Lihua 4; Lin, Pei 4; Park, Richard W. 18; Nazaire, Marc-Danie 4; Robinson, Jim 4; Thorvaldsdottir, Helga 4; Mesirov, Jill 4; Genome Data Analysis Center Institute for Systems Biology; Thorsson, Vesteinn 32; Reynolds, Sheila M. 32; Bernard, Brady 32; Kreisberg, Richard 32; Lin, Jake 32; Iype, Lisa 32; Bressler, Ryan 32; Erkkila, Timo 32; Gundapuneni, Madhumati 32; Liu, Yuexin 33; Norberg, Adam 32; Robinson, Tom 32; Yang, Da 33; Zhang, Wei 33; Shmulevich, Ilya 32; Genome Data Analysis Center Memorial Sloan-Kettering Cancer Center; de Ronde, Jorma J. 34,35; Schultz, Nikolaus 34; Cerami, Ethan 34; Ciriello, Giovanni 34; Goldberg, Arthur P. 34; Gross, Benjamin 34; Jacobsen, Anders 34; Gao, Jianjiong 34; Kaczkowski, Bogumil 34; Sinha, Rileen 34; Aksoy, Arman B. 34; Antipin, Yevgeniy 34; Reva, Boris 34; Shen, Ronglai 36; Taylor, Barry S. 34; Chan, Timothy A. 37,52; Ladanyi, Marc 38; Sander, Chris 34; Genome Data Analysis Center University of Texas MD Anderson Cancer Center; Akbani, Rehan 39; Zhang, Nianxiang 39; Broom, Bradley M. 39; Casasent, Tod 39; Unruh, Anna 39; Wakefield, Chris 39; Hamilton, Stanley R. 33; Cason, Craig R. 33; Baggerly, Keith A. 39; Weinstein, John N. 39,40; Genome Data Analysis Centers, University of California, Santa Cruz and the Buck Institute; Haussler, David 41,42; Benz, Christopher C. 43; Stuart, Joshua M. 41; Benz, Stephen C. 41; Sanborn, Zachary J. 41; Vaske, Charles J. 41; Zhu, Jingchun 41; Szeto, Christopher 41; Scott, Gary K. 43; Yau, Christina 43; Ng, Sam 41; Goldstein, Ted 41; Ellrott, Kyle 41; Collisson, Eric 44; Cozen, Aaron E. 41; Zerbino, Daniel 41; Wilks, Christopher 41; Craft, Brian 41; Spellman, Paul 45; Biospecimen Core Resource International Genomics Consortium; Penny, Robert 46; Shelton, Troy 46; Hatfield, Martha 46; Morris, Scott 46; Yena, Peggy 46; Shelton, Candace 46; Sherman, Mark 46; Paulauskis, Joseph 46; Nationwide Children's Hospital Biospecimen Core Resource; Gastier-Foster, Julie M. 47,48,49; Bowen, Jay 47; Ramirez, Nilsa C. 47,48; Black, Aaron 47; Pyatt, Robert 47,48; Wise, Lisa 47; White, Peter 47,49; Tissue source sites and disease working group; Bertagnolli, Monica 50; Brown, Jen 51; Chu, Gerald C. 53; Czerwinski, Christine 51; Denstman, Fred 54; Dhir, Rajiv 55; Dorner, Arnulf 56; Fuchs, Charles S. 57,58; Guillem, Jose G. 59; Iacocca, Mary 51; Juhl, Hartmut 60; Kaufman, Andrew 52; Kohl, Bernard III 61; Van Le, Xuan 61; Mariano, Maria C. 62; Medina, Elizabeth N. 62; Meyers, Michael 63; Nash, Garrett M. 59; Paty, Phillip B. 59; Petrelli, Nicholas 54; Rabeno, Brenda 51; Richards, William G. 64; Solit, David 66; Swanson, Pat 51; Temple, Larissa 52; Tepper, Joel E. 65; Thorp, Richard 61; Vakiani, Efsevia 62; Weiser, Martin R. 59; Willis, Joseph E. 67; Witkin, Gary 51; Zeng, Zhaoshi 59; Zinner, Michael J. 63; Zornig, Carsten 68; Data-Coordination Center; Jensen, Mark A. 69; Sfeir, Robert 69; Kahn, Ari B. 69; Chu, Anna L. 69; Kothiyal, Prachi 69; Wang, Zhining 69; Snyder, Eric E. 69; Pontius, Joan 69; Pihl, Todd D. 69; Ayala, Brenda 69; Backus, Mark 69; Walton, Jessica 69; Whitmore, Jon 69; Baboud, Julien 69; Berton, Dominique L. 69; Nicholls, Matthew C. 69; Srinivasan, Deepak 69; Raman, Rohini 69; Girshik, Stanley 69; Kigonya, Peter A. 69; Alonso, Shelley 69; Sanbhadti, Rashmi N. 69; Barletta, Sean P. 69; Greene, John M. 69; Pot, David A. 69; Project Team National Cancer Institute; Mills Shaw, Kenna R. 70; Dillon, Laura A. L. 70; Buetow, Ken 71; Davidsen, Tanja 71; Demchok, John A. 70; Eley, Greg 72; Ferguson, Martin 73; Fielding, Peter 70; Schaefer, Carl 71; Sheth, Margi 70; Yang, Liming 70; Project Team National Human Genome Research Institute; Guyer, Mark S. 74; Ozenberger, Bradley A. 74; Palchik, Jacqueline D. 74; Peterson, Jane 74; Sofia, Heidi J. 74; Thomson , Elizabeth 74
[Article]
Nature.
487(7407):330-337, July 19, 2012.
(Format: HTML, PDF)
: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase [epsilon] (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
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