Comprehensive molecular characterization of human colon and rectal cancer

被引：5842

作者：

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 ^{[3
]}

Donehower, Lawrence A. ^{[2
]}

Creighton, Chad J. ^{[2
]}

Wheeler, David A.

Gibbs, Richard A.

Lawrence, Michael S. ^{[4
]}

Voet, Douglas ^{[4
,5
]}

Jing, Rui ^{[4
,5
]}

Cibulskis, Kristian ^{[4
,5
]}

Sivachenko, Andrey ^{[2
,4
,5
]}

Stojanov, Petar ^{[4
,5
]}

McKenna, Aaron ^{[4
,5
]}

Lander, Eric S. ^{[4
,5
,6
,7
]}

Gabriel, Stacey ^{[4
,5
]}

Getz, Gad ^{[4
,5
]}

Ding, Li ^{[8
,9
]}

Fulton, Robert S. ^{[8
]}

Koboldt, Daniel C. ^{[8
]}

Wylie, Todd ^{[8
]}

Walker, Jason ^{[8
]}

Dooling, David J. ^{[8
,9
]}

Fulton, Lucinda ^{[8
]}

Delehaunty, Kim D. ^{[8
]}

Fronick, Catrina C. ^{[8
]}

Demeter, Ryan ^{[8
]}

Mardis, Elaine R. ^{[8
,9
,10
]}

Wilson, Richard K. ^{[8
,9
,10
]}

Chu, Andy ^{[11
]}

Chun, Hye-Jung E. ^{[11
]}

Mungall, Andrew J. ^{[11
]}

Pleasance, Erin ^{[11
]}

Robertson, A. Gordon ^{[11
]}

Stoll, Dominik ^{[11
]}

Balasundaram, Miruna ^{[11
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Baylor Coll Med, Human Genome Sequencing Ctr, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[3] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA

[4] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA

[5] Harvard Univ, Cambridge, MA 02142 USA

[6] MIT, Dept Biol, Cambridge, MA 02142 USA

[7] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA

[8] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA

[9] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA

[10] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA

[11] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[12] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[13] Dana Farber Canc Inst, Dept Med Oncol, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA

[14] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[15] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA

[16] Childrens Hosp, Informat Program, Boston, MA 02115 USA

[17] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[18] Univ N Carolina, Inst Pharmacogenet & Individualized Therapy, Chapel Hill, NC 27599 USA

[19] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[20] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA

[21] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[22] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA

[23] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA

[24] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA

[25] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC USA

[26] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90089 USA

[27] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Div Canc Biol, Baltimore, MD 21231 USA

[28] Inst Syst Biol, Seattle, WA 98109 USA

[29] Univ Texas MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA

[30] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA

[31] Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands

[32] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA

[33] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, Dept Pathol, New York, NY 10065 USA

[34] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[35] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[36] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA

[37] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[38] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA

[39] Buck Inst Age Res, Novato, CA 94945 USA

[40] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA

[41] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA

[42] Int Genom Consortium, Phoenix, AZ 85004 USA

[43] Nationwide Childrens Hosp, Res Inst, Nationwide Childrens Hosp Biospecimen Core Resour, Columbus, OH 43205 USA

[44] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43205 USA

[45] Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43205 USA

[46] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

[47] Christiana Care Hlth Syst, Dept Pathol, Newark, DE 19718 USA

[48] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Brookline, MA 02115 USA

[49] Helen F Graham Canc Ctr Christiana Care, Dept Surg, Newark, DC 19718 USA

[50] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA

来源：

NATURE | 2012年 / 487卷 / 7407期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

SOMATIC MUTATIONS; HUMAN BREAST; GENE; DIFFERENTIATION; WTX; SEQUENCES; ONCOGENE; NETWORK; SOX9; IGF2;

D O I：

10.1038/nature11252

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 e (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.

引用

页码：330 / 337

页数：8

共 44 条

[1] CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER [J].

AALTONEN, LA ;

PELTOMAKI, P ;

LEACH, FS ;

SISTONEN, P ;

PYLKKANEN, L ;

MECKLIN, JP ;

JARVINEN, H ;

POWELL, SM ;

JEN, J ;

HAMILTON, SR ;

PETERSEN, GM ;

KINZLER, KW ;

VOGELSTEIN, B ;

DELACHAPELLE, A .

SCIENCE, 1993, 260 (5109) :812-816

[2] Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion [J].

Bass, Adam J. ;

Lawrence, Michael S. ;

Brace, Lear E. ;

Ramos, Alex H. ;

Drier, Yotam ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Voet, Douglas ;

Saksena, Gordon ;

Sivachenko, Andrey ;

Jing, Rui ;

Parkin, Melissa ;

Pugh, Trevor ;

Verhaak, Roel G. ;

Stransky, Nicolas ;

Boutin, Adam T. ;

Barretina, Jordi ;

Solit, David B. ;

Vakiani, Evi ;

Shao, Wenlin ;

Mishina, Yuji ;

Warmuth, Markus ;

Jimenez, Jose ;

Chiang, Derek Y. ;

Signoretti, Sabina ;

Kaelin, William G., Jr. ;

Spardy, Nicole ;

Hahn, William C. ;

Hoshida, Yujin ;

Ogino, Shuji ;

DePinho, Ronald A. ;

Chin, Lynda ;

Garraway, Levi A. ;

Fuchs, Charles S. ;

Baselga, Jose ;

Tabernero, Josep ;

Gabriel, Stacey ;

Lander, Eric S. ;

Getz, Gad ;

Meyerson, Matthew .

NATURE GENETICS, 2011, 43 (10) :964-U67

[3] Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium [J].

Bastide, Pauline ;

Darido, Charbel ;

Pannequiri, Julie ;

Kist, Ralf ;

Robine, Sylvie ;

Marty-Double, Christiane ;

Bibeau, Frederic ;

Scherer, Gerd ;

Joubert, Dominique ;

Hollande, Frederic ;

Blache, Philippe ;

Jay, Philippe .

JOURNAL OF CELL BIOLOGY, 2007, 178 (04) :635-648

[4] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[5] Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma [J].

Beroukhim, Rameen ;

Getz, Gad ;

Nghiemphu, Leia ;

Barretina, Jordi ;

Hsueh, Teli ;

Linhart, David ;

Vivanco, Igor ;

Lee, Jeffrey C. ;

Huang, Julie H. ;

Alexander, Sethu ;

Du, Jinyan ;

Kau, Tweeny ;

Thomas, Roman K. ;

Shah, Kinial ;

Soto, Horacio ;

Perner, Sven ;

Prensner, John ;

Debiasi, Ralph M. ;

Demichelis, Francesca ;

Hatton, Charlie ;

Rubin, Mark A. ;

Garraway, Levi A. ;

Nelson, Stan F. ;

Liau, Linda ;

Mischel, Paul S. ;

Cloughesy, Tim F. ;

Meyerson, Matthew ;

Golub, Todd A. ;

Lander, Eric S. ;

Mellinghoff, Ingo K. ;

Sellers, William R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (50) :20007-20012

[6] Distinct p53 Transcriptional Programs Dictate Acute DNA-Damage Responses and Tumor Suppression [J].

Brady, Colleen A. ;

Jiang, Dadi ;

Mello, Stephano S. ;

Johnson, Thomas M. ;

Jarvis, Lesley A. ;

Kozak, Margaret M. ;

Broz, Daniela Kenzelmann ;

Basak, Shashwati ;

Park, Eunice J. ;

McLaughlin, Margaret E. ;

Karnezis, Anthony N. ;

Attardi, Laura D. .

CELL, 2011, 145 (04) :571-583

[7] Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer [J].

Camps, Jordi ;

Nguyen, Quang Tri ;

Padilla-Nash, Hesed M. ;

Knutsen, Turid ;

McNeil, Nicole E. ;

Wangsa, Danny ;

Hummon, Amanda B. ;

Grade, Marian ;

Ried, Thomas ;

Difilippantonio, Michael J. .

GENES CHROMOSOMES & CANCER, 2009, 48 (11) :1002-1017

[8] Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer [J].

Chen, Baozhi ;

Dodge, Michael E. ;

Tang, Wei ;

Lu, Jianming ;

Ma, Zhiqiang ;

Fan, Chih-Wei ;

Wei, Shuguang ;

Hao, Wayne ;

Kilgore, Jessica ;

Williams, Noelle S. ;

Roth, Michael G. ;

Amatruda, James F. ;

Chen, Chuo ;

Lum, Lawrence .

NATURE CHEMICAL BIOLOGY, 2009, 5 (02) :100-107

[9]

Chen K, 2009, NAT METHODS, V6, P677, DOI [10.1038/NMETH.1363, 10.1038/nmeth.1363]

[10] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

← 1 2 3 4 5 →