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. Wheeler & 293 others Richard 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, Kenneth 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

3624 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Rectal Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Mutation
Genome
Exome
Microsatellite Instability
Genetic Translocation
DNA Mismatch Repair
MicroRNAs
Methylation
Transcriptional Activation
Genes
Messenger RNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Muzny, D. M., Bainbridge, M. N., Chang, K., Dinh, H. H., Drummond, J. A., Fowler, G., ... Thomson., E. (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487(7407), 330-337. https://doi.org/10.1038/nature11252

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

In: Nature, Vol. 487, No. 7407, 19.07.2012, p. 330-337.

Research output: Contribution to journalArticle

Muzny, DM, Bainbridge, MN, Chang, K, Dinh, HH, Drummond, JA, Fowler, G, Kovar, CL, Lewis, LR, Morgan, MB, Newsham, IF, Reid, JG, Santibanez, J, Shinbrot, E, Trevino, LR, Wu, YQ, Wang, M, Gunaratne, P, Donehower, LA, Creighton, CJ, Wheeler, DA, Gibbs, RA, Lawrence, MS, Voet, D, Jing, R, Cibulskis, K, Sivachenko, A, Stojanov, P, McKenna, A, Lander, ES, Gabriel, S, Ding, L, Fulton, RS, Koboldt, DC, Wylie, T, Walker, J, Dooling, DJ, Fulton, L, Delehaunty, KD, Fronick, CC, Demeter, R, Mardis, ER, Wilson, RK, Chu, A, Chun, HJE, Mungall, AJ, Pleasance, E, Gordon Robertson, A, Stoll, D, Balasundaram, M, Birol, I, Butterfield, YSN, Chuah, E, Coope, RJN, Dhalla, N, Guin, R, Hirst, C, Hirst, M, Holt, RA, Lee, D, Li, HI, Mayo, M, Moore, RA, Schein, JE, Slobodan, JR, Tam, A, Thiessen, N, Varhol, R, Zeng, T, Zhao, Y, Jones, SJM, Marra, MA, Bass, AJ, Ramos, AH, Saksena, G, Cherniack, AD, Schumacher, SE, Tabak, B, Carter, SL, Pho, NH, Nguyen, H, Onofrio, RC, Crenshaw, A, Ardlie, K, Beroukhim, R, Winckler, W, Meyerson, M, Protopopov, A, Hadjipanayis, A, Lee, E, Xi, R, Yang, L, Ren, X, Sathiamoorthy, N, Chen, PC, Haseley, P, Xiao, Y, Lee, S, Seidman, J, Chin, L, Park, PJ, Kucherlapati, R, Todd Auman, J, Hoadley, KA, Du, Y, Wilkerson, MD, Shi, Y, Liquori, C, Meng, S, Li, L, Turman, YJ, Topal, MD, Tan, D, Waring, S, Buda, E, Walsh, J, Jones, CD, Mieczkowski, PA, Singh, D, Wu, J, Gulabani, A, Dolina, P, Bodenheimer, T, Hoyle, AP, Simons, JV, Soloway, M, Mose, LE, Jefferys, SR, Balu, S, O'Connor, BD, Prins, JF, Chiang, DY, Neil Hayes, D, Perou, CM, Hinoue, T, Weisenberger, DJ, Maglinte, DT, Pan, F, Berman, BP, Van Den Berg, DJ, Shen, H, Triche, T, Baylin, SB, Laird, PW, Getz, G, Noble, M, Voat, D, Gehlenborg, N, Dicara, D, Zhang, J, Zhang, H, Wu, CJ, Liu, SY, Shukla, S, Zhou, L, Lin, P, Park, RW, Nazaire, MD, Robinson, J, Thorvaldsdottir, H, Mesirov, J, Thorsson, V, Reynolds, SM, Bernard, B, Kreisberg, R, Lin, J, Iype, L, Bressler, R, Erkkilä, T, Gundapuneni, M, Liu, Y, Norberg, A, Robinson, T, Yang, D, Zhang, W, Shmulevich, I, De Ronde, JJ, Schultz, N, Cerami, E, Ciriello, G, Goldberg, AP, Gross, B, Jacobsen, A, Gao, J, Kaczkowski, B, Sinha, R, Arman Aksoy, B, Antipin, Y, Reva, B, Shen, R, Taylor, BS, Ladanyi, M, Sander, C, Akbani, R, Zhang, N, Broom, BM, Casasent, T, Unruh, A, Wakefield, C, Hamilton, SR, Craig Cason, R, Baggerly, KA, Weinstein, JN, Haussler, D, Benz, CC, Stuart, JM, Benz, SC, Zachary Sanborn, J, Vaske, CJ, Zhu, J, Szeto, C, Scott, GK, Yau, C, Ng, S, Goldstein, T, Ellrott, K, Collisson, E, Cozen, AE, Zerbino, D, Wilks, C, Craft, B, Spellman, P, Penny, R, Shelton, T, Hatfield, M, Morris, S, Yena, P, Shelton, C, Sherman, M, Paulauskis, J, Gastier-Foster, JM, Bowen, J, Ramirez, NC, Black, A, Pyatt, R, Wise, L, White, P, Bertagnolli, M, Brown, J, Chan, TA, Chu, GC, Czerwinski, C, Denstman, F, Dhir, R, Dörner, A, Fuchs, CS, Guillem, JG, Iacocca, M, Juhl, H, Kaufman, A, Iii, BK, Van Le, X, Mariano, MC, Medina, EN, Meyers, M, Nash, GM, Paty, PB, Petrelli, N, Rabeno, B, Richards, WG, Solit, D, Swanson, P, Temple, L, Tepper, JE, Thorp, R, Vakiani, E, Weiser, MR, Willis, JE, Witkin, G, Zeng, Z, Zinner, MJ, Zornig, C, Jensen, MA, Sfeir, R, Kahn, AB, Chu, AL, Kothiyal, P, Wang, Z, Snyder, EE, Pontius, J, Pihl, TD, Ayala, B, Backus, M, Walton, J, Whitmore, J, Baboud, J, Berton, DL, Nicholls, MC, Srinivasan, D, Raman, R, Girshik, S, Kigonya, PA, Alonso, S, Sanbhadti, RN, Barletta, SP, Greene, JM, Pot, DA, Shaw, KRM, Dillon, LAL, Buetow, K, Davidsen, T, Demchok, JA, Eley, G, Ferguson, M, Fielding, P, Schaefer, C, Sheth, M, Yang, L, Guyer, MS, Ozenberger, BA, Palchik, JD, Peterson, J, Sofia, HJ & Thomson., E 2012, 'Comprehensive molecular characterization of human colon and rectal cancer', Nature, vol. 487, no. 7407, pp. 330-337. https://doi.org/10.1038/nature11252
Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G et al. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012 Jul 19;487(7407):330-337. https://doi.org/10.1038/nature11252
Muzny, Donna M. ; Bainbridge, Matthew N. ; Chang, Kyle ; Dinh, Huyen H. ; Drummond, Jennifer A. ; Fowler, Gerald ; Kovar, Christie L. ; Lewis, Lora R. ; Morgan, Margaret B. ; Newsham, Irene F. ; Reid, Jeffrey G. ; Santibanez, Jireh ; Shinbrot, Eve ; Trevino, Lisa R. ; Wu, Yuan Qing ; Wang, Min ; Gunaratne, Preethi ; Donehower, Lawrence A. ; Creighton, Chad J. ; Wheeler, David A. ; Gibbs, Richard A. ; Lawrence, Michael S. ; Voet, Douglas ; Jing, Rui ; Cibulskis, Kristian ; Sivachenko, Andrey ; Stojanov, Petar ; McKenna, Aaron ; Lander, Eric S. ; Gabriel, Stacey ; Ding, Li ; Fulton, Robert S. ; Koboldt, Daniel C. ; Wylie, Todd ; Walker, Jason ; Dooling, David J. ; Fulton, Lucinda ; Delehaunty, Kim D. ; Fronick, Catrina C. ; Demeter, Ryan ; Mardis, Elaine R. ; Wilson, Richard K. ; Chu, Andy ; Chun, Hye Jung E ; Mungall, Andrew J. ; Pleasance, Erin ; Gordon Robertson, A. ; Stoll, Dominik ; Balasundaram, Miruna ; Birol, Inanc ; Butterfield, Yaron S N ; Chuah, Eric ; Coope, Robin J N ; Dhalla, Noreen ; Guin, Ranabir ; Hirst, Carrie ; Hirst, Martin ; Holt, Robert A. ; Lee, Darlene ; Li, Haiyan I. ; Mayo, Michael ; Moore, Richard A. ; Schein, Jacqueline E. ; Slobodan, Jared R. ; Tam, Angela ; Thiessen, Nina ; Varhol, Richard ; Zeng, Thomas ; Zhao, Yongjun ; Jones, Steven J M ; Marra, Marco A. ; Bass, Adam J. ; Ramos, Alex H. ; 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 ; Meyerson, Matthew ; Protopopov, Alexei ; Hadjipanayis, Angela ; Lee, Eunjung ; Xi, Ruibin ; Yang, Lixing ; Ren, Xiaojia ; Sathiamoorthy, Narayanan ; Chen, Peng Chieh ; Haseley, Psalm ; Xiao, Yonghong ; Lee, Semin ; Seidman, Jonathan ; Chin, Lynda ; Park, Peter J. ; Kucherlapati, Raju ; Todd Auman, J. ; Hoadley, Katherine A. ; Du, Ying ; 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 ; Mose, Lisle E. ; Jefferys, Stuart R. ; Balu, Saianand ; O'Connor, Brian D. ; Prins, Jan F. ; Chiang, Derek Y. ; Neil Hayes, D. ; Perou, Charles M. ; Hinoue, Toshinori ; Weisenberger, Daniel J. ; Maglinte, Dennis T. ; Pan, Fei ; Berman, Benjamin P. ; Van Den Berg, David J. ; Shen, Hui ; Triche, Timothy ; Baylin, Stephen B. ; Laird, Peter W. ; Getz, Gad ; Noble, Michael ; Voat, Doug ; Gehlenborg, Nils ; Dicara, Daniel ; Zhang, Juinhua ; Zhang, Hailei ; Wu, Chang Jiun ; Liu, Spring Yingchun ; Shukla, Sachet ; Zhou, Lihua ; Lin, Pei ; Park, Richard W. ; Nazaire, Marc Danie ; Robinson, Jim ; Thorvaldsdottir, Helga ; Mesirov, Jill ; Thorsson, Vesteinn ; Reynolds, Sheila M. ; Bernard, Brady ; Kreisberg, Richard ; Lin, Jake ; Iype, Lisa ; Bressler, Ryan ; Erkkilä, Timo ; Gundapuneni, Madhumati ; Liu, Yuexin ; Norberg, Adam ; Robinson, Tom ; Yang, Da ; Zhang, Wei ; Shmulevich, Ilya ; De Ronde, Jorma J. ; Schultz, Nikolaus ; Cerami, Ethan ; Ciriello, Giovanni ; Goldberg, Arthur P. ; Gross, Benjamin ; Jacobsen, Anders ; Gao, Jianjiong ; Kaczkowski, Bogumil ; Sinha, Rileen ; Arman Aksoy, B. ; Antipin, Yevgeniy ; Reva, Boris ; Shen, Ronglai ; Taylor, Barry S. ; Ladanyi, Marc ; Sander, Chris ; Akbani, Rehan ; Zhang, Nianxiang ; Broom, Bradley M. ; Casasent, Tod ; Unruh, Anna ; Wakefield, Chris ; Hamilton, Stanley R. ; Craig Cason, R. ; Baggerly, Keith A. ; Weinstein, John N. ; Haussler, David ; Benz, Christopher C. ; Stuart, Joshua M. ; Benz, Stephen C. ; Zachary Sanborn, J. ; Vaske, Charles J. ; Zhu, Jingchun ; Szeto, Christopher ; Scott, Gary K. ; Yau, Christina ; Ng, Sam ; Goldstein, Ted ; Ellrott, Kyle ; Collisson, Eric ; Cozen, Aaron E. ; Zerbino, Daniel ; Wilks, Christopher ; Craft, Brian ; Spellman, Paul ; Penny, Robert ; Shelton, Troy ; Hatfield, Martha ; Morris, Scott ; Yena, Peggy ; Shelton, Candace ; Sherman, Mark ; Paulauskis, Joseph ; Gastier-Foster, Julie M. ; Bowen, Jay ; Ramirez, Nilsa C. ; Black, Aaron ; Pyatt, Robert ; Wise, Lisa ; White, Peter ; Bertagnolli, Monica ; Brown, Jen ; Chan, Timothy A. ; Chu, Gerald C. ; Czerwinski, Christine ; Denstman, Fred ; Dhir, Rajiv ; Dörner, Arnulf ; Fuchs, Charles S. ; Guillem, Jose G. ; Iacocca, Mary ; Juhl, Hartmut ; Kaufman, Andrew ; Iii, Bernard Kohl ; Van Le, Xuan ; Mariano, Maria C. ; Medina, Elizabeth N. ; Meyers, Michael ; Nash, Garrett M. ; Paty, Phillip B. ; Petrelli, Nicholas ; Rabeno, Brenda ; Richards, William G. ; Solit, David ; Swanson, Pat ; Temple, Larissa ; Tepper, Joel E. ; Thorp, Richard ; Vakiani, Efsevia ; Weiser, Martin R. ; Willis, Joseph E. ; Witkin, Gary ; Zeng, Zhaoshi ; Zinner, Michael J. ; Zornig, Carsten ; 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 ; Whitmore, Jon ; 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. ; Shaw, Kenna R Mills ; Dillon, Laura A L ; Buetow, Kenneth ; Davidsen, Tanja ; Demchok, John A. ; Eley, Greg ; Ferguson, Martin ; Fielding, Peter ; Schaefer, Carl ; Sheth, Margi ; Yang, Liming ; Guyer, Mark S. ; Ozenberger, Bradley A. ; Palchik, Jacqueline D. ; Peterson, Jane ; Sofia, Heidi J. ; Thomson., Elizabeth. / Comprehensive molecular characterization of human colon and rectal cancer. In: Nature. 2012 ; Vol. 487, No. 7407. pp. 330-337.
@article{199719b5fb4a470788fba9d577b455d0,
title = "Comprehensive molecular characterization of human colon and rectal cancer",
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.",
author = "Muzny, {Donna M.} and Bainbridge, {Matthew N.} and Kyle Chang and Dinh, {Huyen H.} and Drummond, {Jennifer A.} and Gerald Fowler and Kovar, {Christie L.} and Lewis, {Lora R.} and Morgan, {Margaret B.} and Newsham, {Irene F.} and Reid, {Jeffrey G.} and Jireh Santibanez and Eve Shinbrot and Trevino, {Lisa R.} and Wu, {Yuan Qing} and Min Wang and Preethi Gunaratne and Donehower, {Lawrence A.} and Creighton, {Chad J.} and Wheeler, {David A.} and Gibbs, {Richard A.} and Lawrence, {Michael S.} and Douglas Voet and Rui Jing and Kristian Cibulskis and Andrey Sivachenko and Petar Stojanov and Aaron McKenna and Lander, {Eric S.} and Stacey Gabriel and Li Ding and Fulton, {Robert S.} and Koboldt, {Daniel C.} and Todd Wylie and Jason Walker and Dooling, {David J.} and Lucinda Fulton and Delehaunty, {Kim D.} and Fronick, {Catrina C.} and Ryan Demeter and Mardis, {Elaine R.} and Wilson, {Richard K.} and Andy Chu and Chun, {Hye Jung E} and Mungall, {Andrew J.} and Erin Pleasance and {Gordon Robertson}, A. and Dominik Stoll and Miruna Balasundaram and Inanc Birol and Butterfield, {Yaron S N} and Eric Chuah and Coope, {Robin J N} and Noreen Dhalla and Ranabir Guin and Carrie Hirst and Martin Hirst and Holt, {Robert A.} and Darlene Lee and Li, {Haiyan I.} and Michael Mayo and Moore, {Richard A.} and Schein, {Jacqueline E.} and Slobodan, {Jared R.} and Angela Tam and Nina Thiessen and Richard Varhol and Thomas Zeng and Yongjun Zhao and Jones, {Steven J M} and Marra, {Marco A.} and Bass, {Adam J.} and Ramos, {Alex H.} and Gordon Saksena and Cherniack, {Andrew D.} and Schumacher, {Stephen E.} and Barbara Tabak and Carter, {Scott L.} and Pho, {Nam H.} and Huy Nguyen and Onofrio, {Robert C.} and Andrew Crenshaw and Kristin Ardlie and Rameen Beroukhim and Wendy Winckler and Matthew Meyerson and Alexei Protopopov and Angela Hadjipanayis and Eunjung Lee and Ruibin Xi and Lixing Yang and Xiaojia Ren and Narayanan Sathiamoorthy and Chen, {Peng Chieh} and Psalm Haseley and Yonghong Xiao and Semin Lee and Jonathan Seidman and Lynda Chin and Park, {Peter J.} and Raju Kucherlapati and {Todd Auman}, J. and Hoadley, {Katherine A.} and Ying Du and Wilkerson, {Matthew D.} and Yan Shi and Christina Liquori and Shaowu Meng and Ling Li and Turman, {Yidi J.} and Topal, {Michael D.} and Donghui Tan and Scot Waring and Elizabeth Buda and Jesse Walsh and Jones, {Corbin D.} and Mieczkowski, {Piotr A.} and Darshan Singh and Junyuan Wu and Anisha Gulabani and Peter Dolina and Tom Bodenheimer and Hoyle, {Alan P.} and Simons, {Janae V.} and Matthew Soloway and Mose, {Lisle E.} and Jefferys, {Stuart R.} and Saianand Balu and O'Connor, {Brian D.} and Prins, {Jan F.} and Chiang, {Derek Y.} and {Neil Hayes}, D. and Perou, {Charles M.} and Toshinori Hinoue and Weisenberger, {Daniel J.} and Maglinte, {Dennis T.} and Fei Pan and Berman, {Benjamin P.} and {Van Den Berg}, {David J.} and Hui Shen and Timothy Triche and Baylin, {Stephen B.} and Laird, {Peter W.} and Gad Getz and Michael Noble and Doug Voat and Nils Gehlenborg and Daniel Dicara and Juinhua Zhang and Hailei Zhang and Wu, {Chang Jiun} and Liu, {Spring Yingchun} and Sachet Shukla and Lihua Zhou and Pei Lin and Park, {Richard W.} and Nazaire, {Marc Danie} and Jim Robinson and Helga Thorvaldsdottir and Jill Mesirov and Vesteinn Thorsson and Reynolds, {Sheila M.} and Brady Bernard and Richard Kreisberg and Jake Lin and Lisa Iype and Ryan Bressler and Timo Erkkil{\"a} and Madhumati Gundapuneni and Yuexin Liu and Adam Norberg and Tom Robinson and Da Yang and Wei Zhang and Ilya Shmulevich and {De Ronde}, {Jorma J.} and Nikolaus Schultz and Ethan Cerami and Giovanni Ciriello and Goldberg, {Arthur P.} and Benjamin Gross and Anders Jacobsen and Jianjiong Gao and Bogumil Kaczkowski and Rileen Sinha and {Arman Aksoy}, B. and Yevgeniy Antipin and Boris Reva and Ronglai Shen and Taylor, {Barry S.} and Marc Ladanyi and Chris Sander and Rehan Akbani and Nianxiang Zhang and Broom, {Bradley M.} and Tod Casasent and Anna Unruh and Chris Wakefield and Hamilton, {Stanley R.} and {Craig Cason}, R. and Baggerly, {Keith A.} and Weinstein, {John N.} and David Haussler and Benz, {Christopher C.} and Stuart, {Joshua M.} and Benz, {Stephen C.} and {Zachary Sanborn}, J. and Vaske, {Charles J.} and Jingchun Zhu and Christopher Szeto and Scott, {Gary K.} and Christina Yau and Sam Ng and Ted Goldstein and Kyle Ellrott and Eric Collisson and Cozen, {Aaron E.} and Daniel Zerbino and Christopher Wilks and Brian Craft and Paul Spellman and Robert Penny and Troy Shelton and Martha Hatfield and Scott Morris and Peggy Yena and Candace Shelton and Mark Sherman and Joseph Paulauskis and Gastier-Foster, {Julie M.} and Jay Bowen and Ramirez, {Nilsa C.} and Aaron Black and Robert Pyatt and Lisa Wise and Peter White and Monica Bertagnolli and Jen Brown and Chan, {Timothy A.} and Chu, {Gerald C.} and Christine Czerwinski and Fred Denstman and Rajiv Dhir and Arnulf D{\"o}rner and Fuchs, {Charles S.} and Guillem, {Jose G.} and Mary Iacocca and Hartmut Juhl and Andrew Kaufman and Iii, {Bernard Kohl} and {Van Le}, Xuan and Mariano, {Maria C.} and Medina, {Elizabeth N.} and Michael Meyers and Nash, {Garrett M.} and Paty, {Phillip B.} and Nicholas Petrelli and Brenda Rabeno and Richards, {William G.} and David Solit and Pat Swanson and Larissa Temple and Tepper, {Joel E.} and Richard Thorp and Efsevia Vakiani and Weiser, {Martin R.} and Willis, {Joseph E.} and Gary Witkin and Zhaoshi Zeng and Zinner, {Michael J.} and Carsten Zornig and Jensen, {Mark A.} and Robert Sfeir and Kahn, {Ari B.} and Chu, {Anna L.} and Prachi Kothiyal and Zhining Wang and Snyder, {Eric E.} and Joan Pontius and Pihl, {Todd D.} and Brenda Ayala and Mark Backus and Jessica Walton and Jon Whitmore and Julien Baboud and Berton, {Dominique L.} and Nicholls, {Matthew C.} and Deepak Srinivasan and Rohini Raman and Stanley Girshik and Kigonya, {Peter A.} and Shelley Alonso and Sanbhadti, {Rashmi N.} and Barletta, {Sean P.} and Greene, {John M.} and Pot, {David A.} and Shaw, {Kenna R Mills} and Dillon, {Laura A L} and Kenneth Buetow and Tanja Davidsen and Demchok, {John A.} and Greg Eley and Martin Ferguson and Peter Fielding and Carl Schaefer and Margi Sheth and Liming Yang and Guyer, {Mark S.} and Ozenberger, {Bradley A.} and Palchik, {Jacqueline D.} and Jane Peterson and Sofia, {Heidi J.} and Elizabeth Thomson.",
year = "2012",
month = "7",
day = "19",
doi = "10.1038/nature11252",
language = "English (US)",
volume = "487",
pages = "330--337",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7407",

}

TY - JOUR

T1 - Comprehensive molecular characterization of human colon and rectal cancer

AU - Muzny, Donna M.

AU - Bainbridge, Matthew N.

AU - Chang, Kyle

AU - Dinh, Huyen H.

AU - Drummond, Jennifer A.

AU - Fowler, Gerald

AU - Kovar, Christie L.

AU - Lewis, Lora R.

AU - Morgan, Margaret B.

AU - Newsham, Irene F.

AU - Reid, Jeffrey G.

AU - Santibanez, Jireh

AU - Shinbrot, Eve

AU - Trevino, Lisa R.

AU - Wu, Yuan Qing

AU - Wang, Min

AU - Gunaratne, Preethi

AU - Donehower, Lawrence A.

AU - Creighton, Chad J.

AU - Wheeler, David A.

AU - Gibbs, Richard A.

AU - Lawrence, Michael S.

AU - Voet, Douglas

AU - Jing, Rui

AU - Cibulskis, Kristian

AU - Sivachenko, Andrey

AU - Stojanov, Petar

AU - McKenna, Aaron

AU - Lander, Eric S.

AU - Gabriel, Stacey

AU - Ding, Li

AU - Fulton, Robert S.

AU - Koboldt, Daniel C.

AU - Wylie, Todd

AU - Walker, Jason

AU - Dooling, David J.

AU - Fulton, Lucinda

AU - Delehaunty, Kim D.

AU - Fronick, Catrina C.

AU - Demeter, Ryan

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

AU - Chu, Andy

AU - Chun, Hye Jung E

AU - Mungall, Andrew J.

AU - Pleasance, Erin

AU - Gordon Robertson, A.

AU - Stoll, Dominik

AU - Balasundaram, Miruna

AU - Birol, Inanc

AU - Butterfield, Yaron S N

AU - Chuah, Eric

AU - Coope, Robin J N

AU - Dhalla, Noreen

AU - Guin, Ranabir

AU - Hirst, Carrie

AU - Hirst, Martin

AU - Holt, Robert A.

AU - Lee, Darlene

AU - Li, Haiyan I.

AU - Mayo, Michael

AU - Moore, Richard A.

AU - Schein, Jacqueline E.

AU - Slobodan, Jared R.

AU - Tam, Angela

AU - Thiessen, Nina

AU - Varhol, Richard

AU - Zeng, Thomas

AU - Zhao, Yongjun

AU - Jones, Steven J M

AU - Marra, Marco A.

AU - Bass, Adam J.

AU - Ramos, Alex H.

AU - Saksena, Gordon

AU - Cherniack, Andrew D.

AU - Schumacher, Stephen E.

AU - Tabak, Barbara

AU - Carter, Scott L.

AU - Pho, Nam H.

AU - Nguyen, Huy

AU - Onofrio, Robert C.

AU - Crenshaw, Andrew

AU - Ardlie, Kristin

AU - Beroukhim, Rameen

AU - Winckler, Wendy

AU - Meyerson, Matthew

AU - Protopopov, Alexei

AU - Hadjipanayis, Angela

AU - Lee, Eunjung

AU - Xi, Ruibin

AU - Yang, Lixing

AU - Ren, Xiaojia

AU - Sathiamoorthy, Narayanan

AU - Chen, Peng Chieh

AU - Haseley, Psalm

AU - Xiao, Yonghong

AU - Lee, Semin

AU - Seidman, Jonathan

AU - Chin, Lynda

AU - Park, Peter J.

AU - Kucherlapati, Raju

AU - Todd Auman, J.

AU - Hoadley, Katherine A.

AU - Du, Ying

AU - Wilkerson, Matthew D.

AU - Shi, Yan

AU - Liquori, Christina

AU - Meng, Shaowu

AU - Li, Ling

AU - Turman, Yidi J.

AU - Topal, Michael D.

AU - Tan, Donghui

AU - Waring, Scot

AU - Buda, Elizabeth

AU - Walsh, Jesse

AU - Jones, Corbin D.

AU - Mieczkowski, Piotr A.

AU - Singh, Darshan

AU - Wu, Junyuan

AU - Gulabani, Anisha

AU - Dolina, Peter

AU - Bodenheimer, Tom

AU - Hoyle, Alan P.

AU - Simons, Janae V.

AU - Soloway, Matthew

AU - Mose, Lisle E.

AU - Jefferys, Stuart R.

AU - Balu, Saianand

AU - O'Connor, Brian D.

AU - Prins, Jan F.

AU - Chiang, Derek Y.

AU - Neil Hayes, D.

AU - Perou, Charles M.

AU - Hinoue, Toshinori

AU - Weisenberger, Daniel J.

AU - Maglinte, Dennis T.

AU - Pan, Fei

AU - Berman, Benjamin P.

AU - Van Den Berg, David J.

AU - Shen, Hui

AU - Triche, Timothy

AU - Baylin, Stephen B.

AU - Laird, Peter W.

AU - Getz, Gad

AU - Noble, Michael

AU - Voat, Doug

AU - Gehlenborg, Nils

AU - Dicara, Daniel

AU - Zhang, Juinhua

AU - Zhang, Hailei

AU - Wu, Chang Jiun

AU - Liu, Spring Yingchun

AU - Shukla, Sachet

AU - Zhou, Lihua

AU - Lin, Pei

AU - Park, Richard W.

AU - Nazaire, Marc Danie

AU - Robinson, Jim

AU - Thorvaldsdottir, Helga

AU - Mesirov, Jill

AU - Thorsson, Vesteinn

AU - Reynolds, Sheila M.

AU - Bernard, Brady

AU - Kreisberg, Richard

AU - Lin, Jake

AU - Iype, Lisa

AU - Bressler, Ryan

AU - Erkkilä, Timo

AU - Gundapuneni, Madhumati

AU - Liu, Yuexin

AU - Norberg, Adam

AU - Robinson, Tom

AU - Yang, Da

AU - Zhang, Wei

AU - Shmulevich, Ilya

AU - De Ronde, Jorma J.

AU - Schultz, Nikolaus

AU - Cerami, Ethan

AU - Ciriello, Giovanni

AU - Goldberg, Arthur P.

AU - Gross, Benjamin

AU - Jacobsen, Anders

AU - Gao, Jianjiong

AU - Kaczkowski, Bogumil

AU - Sinha, Rileen

AU - Arman Aksoy, B.

AU - Antipin, Yevgeniy

AU - Reva, Boris

AU - Shen, Ronglai

AU - Taylor, Barry S.

AU - Ladanyi, Marc

AU - Sander, Chris

AU - Akbani, Rehan

AU - Zhang, Nianxiang

AU - Broom, Bradley M.

AU - Casasent, Tod

AU - Unruh, Anna

AU - Wakefield, Chris

AU - Hamilton, Stanley R.

AU - Craig Cason, R.

AU - Baggerly, Keith A.

AU - Weinstein, John N.

AU - Haussler, David

AU - Benz, Christopher C.

AU - Stuart, Joshua M.

AU - Benz, Stephen C.

AU - Zachary Sanborn, J.

AU - Vaske, Charles J.

AU - Zhu, Jingchun

AU - Szeto, Christopher

AU - Scott, Gary K.

AU - Yau, Christina

AU - Ng, Sam

AU - Goldstein, Ted

AU - Ellrott, Kyle

AU - Collisson, Eric

AU - Cozen, Aaron E.

AU - Zerbino, Daniel

AU - Wilks, Christopher

AU - Craft, Brian

AU - Spellman, Paul

AU - Penny, Robert

AU - Shelton, Troy

AU - Hatfield, Martha

AU - Morris, Scott

AU - Yena, Peggy

AU - Shelton, Candace

AU - Sherman, Mark

AU - Paulauskis, Joseph

AU - Gastier-Foster, Julie M.

AU - Bowen, Jay

AU - Ramirez, Nilsa C.

AU - Black, Aaron

AU - Pyatt, Robert

AU - Wise, Lisa

AU - White, Peter

AU - Bertagnolli, Monica

AU - Brown, Jen

AU - Chan, Timothy A.

AU - Chu, Gerald C.

AU - Czerwinski, Christine

AU - Denstman, Fred

AU - Dhir, Rajiv

AU - Dörner, Arnulf

AU - Fuchs, Charles S.

AU - Guillem, Jose G.

AU - Iacocca, Mary

AU - Juhl, Hartmut

AU - Kaufman, Andrew

AU - Iii, Bernard Kohl

AU - Van Le, Xuan

AU - Mariano, Maria C.

AU - Medina, Elizabeth N.

AU - Meyers, Michael

AU - Nash, Garrett M.

AU - Paty, Phillip B.

AU - Petrelli, Nicholas

AU - Rabeno, Brenda

AU - Richards, William G.

AU - Solit, David

AU - Swanson, Pat

AU - Temple, Larissa

AU - Tepper, Joel E.

AU - Thorp, Richard

AU - Vakiani, Efsevia

AU - Weiser, Martin R.

AU - Willis, Joseph E.

AU - Witkin, Gary

AU - Zeng, Zhaoshi

AU - Zinner, Michael J.

AU - Zornig, Carsten

AU - Jensen, Mark A.

AU - Sfeir, Robert

AU - Kahn, Ari B.

AU - Chu, Anna L.

AU - Kothiyal, Prachi

AU - Wang, Zhining

AU - Snyder, Eric E.

AU - Pontius, Joan

AU - Pihl, Todd D.

AU - Ayala, Brenda

AU - Backus, Mark

AU - Walton, Jessica

AU - Whitmore, Jon

AU - Baboud, Julien

AU - Berton, Dominique L.

AU - Nicholls, Matthew C.

AU - Srinivasan, Deepak

AU - Raman, Rohini

AU - Girshik, Stanley

AU - Kigonya, Peter A.

AU - Alonso, Shelley

AU - Sanbhadti, Rashmi N.

AU - Barletta, Sean P.

AU - Greene, John M.

AU - Pot, David A.

AU - Shaw, Kenna R Mills

AU - Dillon, Laura A L

AU - Buetow, Kenneth

AU - Davidsen, Tanja

AU - Demchok, John A.

AU - Eley, Greg

AU - Ferguson, Martin

AU - Fielding, Peter

AU - Schaefer, Carl

AU - Sheth, Margi

AU - Yang, Liming

AU - Guyer, Mark S.

AU - Ozenberger, Bradley A.

AU - Palchik, Jacqueline D.

AU - Peterson, Jane

AU - Sofia, Heidi J.

AU - Thomson., Elizabeth

PY - 2012/7/19

Y1 - 2012/7/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863922124&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863922124&partnerID=8YFLogxK

U2 - 10.1038/nature11252

DO - 10.1038/nature11252

M3 - Article

VL - 487

SP - 330

EP - 337

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7407

ER -