Comprehensive molecular characterization of human colon and rectal cancer

Donna M. Muzny, Matthew N. Bainbridge, Kyle Chang, Huyen H. Dinh, Jennifer A. Drummond, Gerald Fowler, Christie L. Kovar, Lora R. Lewis, Margaret B. Morgan, Irene F. Newsham, Jeffrey G. Reid, Jireh Santibanez, Eve Shinbrot, Lisa R. Trevino, Yuan Qing Wu, Min Wang, Preethi Gunaratne, Lawrence A. Donehower, Chad J. Creighton, David A. WheelerRichard A. Gibbs, Michael S. Lawrence, Douglas Voet, Rui Jing, Kristian Cibulskis, Andrey Sivachenko, Petar Stojanov, Aaron McKenna, Eric S. Lander, Stacey Gabriel, Li Ding, Robert S. Fulton, Daniel C. Koboldt, Todd Wylie, Jason Walker, David J. Dooling, Lucinda Fulton, Kim D. Delehaunty, Catrina C. Fronick, Ryan Demeter, Elaine R. Mardis, Richard K. Wilson, Andy Chu, Hye Jung E. Chun, Andrew J. Mungall, Erin Pleasance, A. Gordon Robertson, Dominik Stoll, Miruna Balasundaram, Inanc Birol, Yaron S.N. Butterfield, Eric Chuah, Robin J.N. Coope, Noreen Dhalla, Ranabir Guin, Carrie Hirst, Martin Hirst, Robert A. Holt, Darlene Lee, Haiyan I. Li, Michael Mayo, Richard A. Moore, Jacqueline E. Schein, Jared R. Slobodan, Angela Tam, Nina Thiessen, Richard Varhol, Thomas Zeng, Yongjun Zhao, Steven J.M. Jones, Marco A. Marra, Adam J. Bass, Alex H. Ramos, Gordon Saksena, Andrew D. Cherniack, Stephen E. Schumacher, Barbara Tabak, Scott L. Carter, Nam H. Pho, Huy Nguyen, Robert C. Onofrio, Andrew Crenshaw, Kristin Ardlie, Rameen Beroukhim, Wendy Winckler, Matthew Meyerson, Alexei Protopopov, Angela Hadjipanayis, Eunjung Lee, Ruibin Xi, Lixing Yang, Xiaojia Ren, Narayanan Sathiamoorthy, Peng Chieh Chen, Psalm Haseley, Yonghong Xiao, Semin Lee, Jonathan Seidman, Lynda Chin, Peter J. Park, Raju Kucherlapati, J. Todd Auman, Katherine A. Hoadley, Ying Du, Matthew D. Wilkerson, Yan Shi, Christina Liquori, Shaowu Meng, Ling Li, Yidi J. Turman, Michael D. Topal, Donghui Tan, Scot Waring, Elizabeth Buda, Jesse Walsh, Corbin D. Jones, Piotr A. Mieczkowski, Darshan Singh, Junyuan Wu, Anisha Gulabani, Peter Dolina, Tom Bodenheimer, Alan P. Hoyle, Janae V. Simons, Matthew Soloway, Lisle E. Mose, Stuart R. Jefferys, Saianand Balu, Brian D. O'Connor, Jan F. Prins, Derek Y. Chiang, D. Neil Hayes, Charles M. Perou, Toshinori Hinoue, Daniel J. Weisenberger, Dennis T. Maglinte, Fei Pan, Benjamin P. Berman, David J. Van Den Berg, Hui Shen, Timothy Triche, Stephen B. Baylin, Peter W. Laird, Gad Getz, Michael Noble, Doug Voat, Nils Gehlenborg, Daniel Dicara, Juinhua Zhang, Hailei Zhang, Chang Jiun Wu, Spring Yingchun Liu, Sachet Shukla, Lihua Zhou, Pei Lin, Richard W. Park, Marc Danie Nazaire, Jim Robinson, Helga Thorvaldsdottir, Jill Mesirov, Vesteinn Thorsson, Sheila M. Reynolds, Brady Bernard, Richard Kreisberg, Jake Lin, Lisa Iype, Ryan Bressler, Timo Erkkilä, Madhumati Gundapuneni, Yuexin Liu, Adam Norberg, Tom Robinson, Da Yang, Wei Zhang, Ilya Shmulevich, Jorma J. De Ronde, Nikolaus Schultz, Ethan Cerami, Giovanni Ciriello, Arthur P. Goldberg, Benjamin Gross, Anders Jacobsen, Jianjiong Gao, Bogumil Kaczkowski, Rileen Sinha, B. Arman Aksoy, Yevgeniy Antipin, Boris Reva, Ronglai Shen, Barry S. Taylor, Marc Ladanyi, Chris Sander, Rehan Akbani, Nianxiang Zhang, Bradley M. Broom, Tod Casasent, Anna Unruh, Chris Wakefield, Stanley R. Hamilton, R. Craig Cason, Keith A. Baggerly, John N. Weinstein, David Haussler, Christopher C. Benz, Joshua M. Stuart, Stephen C. Benz, J. Zachary Sanborn, Charles J. Vaske, Jingchun Zhu, Christopher Szeto, Gary K. Scott, Christina Yau, Sam Ng, Ted Goldstein, Kyle Ellrott, Eric Collisson, Aaron E. Cozen, Daniel Zerbino, Christopher Wilks, Brian Craft, Paul Spellman, Robert Penny, Troy Shelton, Martha Hatfield, Scott Morris, Peggy Yena, Candace Shelton, Mark Sherman, Joseph Paulauskis, Julie M. Gastier-Foster, Jay Bowen, Nilsa C. Ramirez, Aaron Black, Robert Pyatt, Lisa Wise, Peter White, Monica Bertagnolli, Jen Brown, Timothy A. Chan, Gerald C. Chu, Christine Czerwinski, Fred Denstman, Rajiv Dhir, Arnulf Dörner, Charles S. Fuchs, Jose G. Guillem, Mary Iacocca, Hartmut Juhl, Andrew Kaufman, Bernard Kohl Iii, Xuan Van Le, Maria C. Mariano, Elizabeth N. Medina, Michael Meyers, Garrett M. Nash, Phillip B. Paty, Nicholas Petrelli, Brenda Rabeno, William G. Richards, David Solit, Pat Swanson, Larissa Temple, Joel E. Tepper, Richard Thorp, Efsevia Vakiani, Martin R. Weiser, Joseph E. Willis, Gary Witkin, Zhaoshi Zeng, Michael J. Zinner, Carsten Zornig, Mark A. Jensen, Robert Sfeir, Ari B. Kahn, Anna L. Chu, Prachi Kothiyal, Zhining Wang, Eric E. Snyder, Joan Pontius, Todd D. Pihl, Brenda Ayala, Mark Backus, Jessica Walton, Jon Whitmore, Julien Baboud, Dominique L. Berton, Matthew C. Nicholls, Deepak Srinivasan, Rohini Raman, Stanley Girshik, Peter A. Kigonya, Shelley Alonso, Rashmi N. Sanbhadti, Sean P. Barletta, John M. Greene, David A. Pot, Kenna R.Mills Shaw, Laura A.L. Dillon, Ken Buetow, Tanja Davidsen, John A. Demchok, Greg Eley, Martin Ferguson, Peter Fielding, Carl Schaefer, Margi Sheth, Liming Yang, Mark S. Guyer, Bradley A. Ozenberger, Jacqueline D. Palchik, Jane Peterson, Heidi J. Sofia, Elizabeth Thomson.

Research output: Contribution to journalArticle

Abstract

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 μ (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.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalNature
Volume487
Issue number7407
DOIs
StatePublished - Jul 19 2012

ASJC Scopus subject areas

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    Muzny, D. M., Bainbridge, M. N., Chang, K., Dinh, H. H., Drummond, J. A., Fowler, G., Kovar, C. L., Lewis, L. R., Morgan, M. B., Newsham, I. F., Reid, J. G., Santibanez, J., Shinbrot, E., Trevino, L. R., Wu, Y. Q., Wang, M., Gunaratne, P., Donehower, L. A., Creighton, C. J., ... Thomson., E. (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487(7407), 330-337. https://doi.org/10.1038/nature11252