Emerging landscape of oncogenic signatures across human cancers

被引：986

作者：

Ciriello, Giovanni ^{[1
]}

Miller, Martin L. ^{[1
]}

Aksoy, Buelent Arman ^{[1
]}

Senbabaoglu, Yasin ^{[1
]}

Schultz, Nikolaus ^{[1
]}

Sander, Chris ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10021 USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 10期

基金：

美国国家卫生研究院;

关键词：

MUTATIONS; CTCF; ONCOLOGY; PROMOTER; BINDING; PROTEIN; ARID1A; TARGET; BREAST;

D O I：

10.1038/ng.2762

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cancer therapy is challenged by the diversity of molecular implementations of oncogenic processes and by the resulting variation in therapeutic responses. Projects such as The Cancer Genome Atlas (TCGA) provide molecular tumor maps in unprecedented detail. The interpretation of these maps remains a major challenge. Here we distilled thousands of genetic and epigenetic features altered in cancers to similar to 500 selected functional events (SFEs). Using this simplified description, we derived a hierarchical classification of 3,299 TCGA tumors from 12 cancer types. The top classes are dominated by either mutations (M class) or copy number changes (C class). This distinction is clearest at the extremes of genomic instability, indicating the presence of different oncogenic processes. The full hierarchy shows functional event patterns characteristic of multiple cross-tissue groups of tumors, termed oncogenic signature classes. Targetable functional events in a tumor class are suggestive of class-specific combination therapy. These results may assist in the definition of clinical trials to match actionable oncogenic signatures with personalized therapies.

引用

页码：1127 / U247

页数：9

共 37 条

[1] Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma [J].

Aguirre, Andrew J. ;

Hruban, Ralph H. ;

Raphael, Benjamin J. .

CANCER CELL, 2017, 32 (02) :185-+

[2] Sequence analysis of mutations and translocations across breast cancer subtypes [J].

Banerji, Shantanu ;

Cibulskis, Kristian ;

Rangel-Escareno, Claudia ;

Brown, Kristin K. ;

Carter, Scott L. ;

Frederick, Abbie M. ;

Lawrence, Michael S. ;

Sivachenko, Andrey Y. ;

Sougnez, Carrie ;

Zou, Lihua ;

Cortes, Maria L. ;

Fernandez-Lopez, Juan C. ;

Peng, Shouyong ;

Ardlie, Kristin G. ;

Auclair, Daniel ;

Bautista-Pina, Veronica ;

Duke, Fujiko ;

Francis, Joshua ;

Jung, Joonil ;

Maffuz-Aziz, Antonio ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Pho, Nam H. ;

Quintanar-Jurado, Valeria ;

Ramos, Alex H. ;

Rebollar-Vega, Rosa ;

Rodriguez-Cuevas, Sergio ;

Romero-Cordoba, Sandra L. ;

Schumacher, Steven E. ;

Stransky, Nicolas ;

Thompson, Kristin M. ;

Uribe-Figueroa, Laura ;

Baselga, Jose ;

Beroukhim, Rameen ;

Polyak, Kornelia ;

Sgroi, Dennis C. ;

Richardson, Andrea L. ;

Jimenez-Sanchez, Gerardo ;

Lander, Eric S. ;

Gabriel, Stacey B. ;

Garraway, Levi A. ;

Golub, Todd R. ;

Melendez-Zajgla, Jorge ;

Toker, Alex ;

Getz, Gad ;

Hidalgo-Miranda, Alfredo ;

Meyerson, Matthew .

NATURE, 2012, 486 (7403) :405-409

[3] Modularity and community detection in bipartite networks [J].

Barber, Michael J. .

PHYSICAL REVIEW E, 2007, 76 (06)

[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]

Canc Genome Atlas Res Network, 2012, NATURE, V491, P288, DOI 10.1038/nature11666

[7] Detecting repeated cancer evolution from multiregion tumor sequencing data [J].

Caravagna, Giulio ;

Giarratano, Ylenia ;

Ramazzotti, Daniele ;

Tomlinson, Ian ;

Graham, Trevor A. ;

Sanguinetti, Guido ;

Sottoriva, Andrea .

NATURE METHODS, 2018, 15 (09) :707-+

[8] The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].

Cerami, Ethan ;

Gao, Jianjiong ;

Dogrusoz, Ugur ;

Gross, Benjamin E. ;

Sumer, Selcuk Onur ;

Aksoy, Buelent Arman ;

Jacobsen, Anders ;

Byrne, Caitlin J. ;

Heuer, Michael L. ;

Larsson, Erik ;

Antipin, Yevgeniy ;

Reva, Boris ;

Goldberg, Arthur P. ;

Sander, Chris ;

Schultz, Nikolaus .

CANCER DISCOVERY, 2012, 2 (05) :401-404

[9] Increase of ZASC1 gene copy number in recurrent oral carcinoma [J].

Chiang, W-F ;

Hung, P-S ;

Liu, S-Y ;

Yuan, T-C ;

Chang, K-W ;

Chen, Y-P ;

Liu, Y-C ;

Lin, S-C .

ORAL DISEASES, 2011, 17 (01) :53-59

[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

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