Cumulative Haploinsufficiency and Triplosensitivity Drive Aneuploidy Patterns and Shape the Cancer Genome

被引：609

作者：

Davoli, Teresa ^{[1
,2
]}

Xu, Andrew Wei ^{[2
,4
]}

Mengwasser, Kristen E. ^{[1
,2
]}

Sack, Laura M. ^{[1
,2
]}

Yoon, John C. ^{[2
,3
]}

Park, Peter J. ^{[2
,4
]}

Elledge, Stephen J. ^{[1
,2
]}

机构：

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

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

[3] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

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

来源：

CELL | 2013年 / 155卷 / 04期

关键词：

REVEALS; MUTATIONS; RESOURCE;

D O I：

10.1016/j.cell.2013.10.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aneuploidy has been recognized as a hallmark of cancer for more than 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. Here, we develop Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing >8,200 tumor-normal pairs, we provide statistical evidence suggesting that many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and potency of TSGs (STOP genes), OGs, and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity.

引用

页码：948 / 962

页数：15

共 37 条

[1] A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response [J].

Adamson, Britt ;

Smogorzewska, Agata ;

Sigoillot, Frederic D. ;

King, Randall W. ;

Elledge, Stephen J. .

NATURE CELL BIOLOGY, 2012, 14 (03) :318-+

[2] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[3] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[4] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[5] Y chromosome structural and functional changes in human malignant diseases [J].

Bianchi, Nestor O. .

MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2009, 682 (01) :21-27

[6]

Boveri T., 1929, The origin of malignant tumors

[7] Modulation of autoimmunity by the latest interleukins (with special emphasis on IL-32) [J].

Conti, P. ;

Youinou, P. ;

Theoharides, T. C. .

AUTOIMMUNITY REVIEWS, 2007, 6 (03) :131-137

[8] MuSiC: Identifying mutational significance in cancer genomes [J].

Dees, Nathan D. ;

Zhang, Qunyuan ;

Kandoth, Cyriac ;

Wendl, Michael C. ;

Schierding, William ;

Koboldt, Daniel C. ;

Mooney, Thomas B. ;

Callaway, Matthew B. ;

Dooling, David ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

Ding, Li .

GENOME RESEARCH, 2012, 22 (08) :1589-1598

[9] COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer [J].

Forbes, Simon A. ;

Tang, Gurpreet ;

Bindal, Nidhi ;

Bamford, Sally ;

Dawson, Elisabeth ;

Cole, Charlotte ;

Kok, Chai Yin ;

Jia, Mingming ;

Ewing, Rebecca ;

Menzies, Andrew ;

Teague, Jon W. ;

Stratton, Michael R. ;

Futreal, P. Andrew .

NUCLEIC ACIDS RESEARCH, 2010, 38 :D652-D657

[10] A census of human cancer genes [J].

Futreal, PA ;

Coin, L ;

Marshall, M ;

Down, T ;

Hubbard, T ;

Wooster, R ;

Rahman, N ;

Stratton, MR .

NATURE REVIEWS CANCER, 2004, 4 (03) :177-183

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