The landscape of somatic copy-number alteration across human cancers

Rameen Beroukhim; Craig H. Mermel; Dale Porter; Guo Wei; Soumya Raychaudhuri; Jerry Donovan; Jordi Barretina; Jesse S. Boehm; Jennifer Dobson; Mitsuyoshi Urashima; Kevin T. McHenry; Reid M. Pinchback; Azra H. Ligon; Yoon Jae Cho; Leila Haery; Heidi Greulich; Michael Reich; Wendy Winckler; Michael S. Lawrence; Barbara A. Weir; Kumiko E. Tanaka; Derek Y. Chiang; Adam J. Bass; Alice Loo; Carter Hoffman; John Prensner; Ted Liefeld; Qing Gao; Derek Yecies; Sabina Signoretti; Elizabeth Maher; Frederic J. Kaye; Hidefumi Sasaki; Joel E. Tepper; Jonathan A. Fletcher; Josep Tabernero; José Baselga; Ming Sound Tsao; Francesca Demichelis; Mark A. Rubin; Pasi A. Janne; Mark J. Daly; Carmelo Nucera; Ross L. Levine; Benjamin L. Ebert; Stacey Gabrie; Anil K. Rustgi; Cristina R. Antonescu; Marc Ladanyi; Anthony Letai; Levi A. Garraway; Massimo Loda; David G. Beer; Lawrence D. True; Aikou Okamoto; Scott L. Pomeroy; Samuel Singer; Todd R. Golub; Eric S. Lander; Gad Getz; William R. Sellers; Matthew Meyerson

doi:https://doi.org/10.1038/nature08822

The landscape of somatic copy-number alteration across human cancers

Rameen Beroukhim, Craig H. Mermel, Dale Porter, Guo Wei, Soumya Raychaudhuri, Jerry Donovan, Jordi Barretina, Jesse S. Boehm, Jennifer Dobson, Mitsuyoshi Urashima, Kevin T. McHenry, Reid M. Pinchback, Azra H. Ligon, Yoon Jae Cho, Leila Haery, Heidi Greulich, Michael Reich, Wendy Winckler, Michael S. Lawrence, Barbara A. WeirKumiko E. Tanaka, Derek Y. Chiang, Adam J. Bass, Alice Loo, Carter Hoffman, John Prensner, Ted Liefeld, Qing Gao, Derek Yecies, Sabina Signoretti, Elizabeth Maher, Frederic J. Kaye, Hidefumi Sasaki, Joel E. Tepper, Jonathan A. Fletcher, Josep Tabernero, José Baselga, Ming Sound Tsao, Francesca Demichelis, Mark A. Rubin, Pasi A. Janne, Mark J. Daly, Carmelo Nucera, Ross L. Levine, Benjamin L. Ebert, Stacey Gabrie, Anil K. Rustgi, Cristina R. Antonescu, Marc Ladanyi, Anthony Letai, Levi A. Garraway, Massimo Loda, David G. Beer, Lawrence D. True, Aikou Okamoto, Scott L. Pomeroy, Samuel Singer, Todd R. Golub, Eric S. Lander, Gad Getz, William R. Sellers, Matthew Meyerson

Department of Medicine

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2696 Citations (Scopus)

Abstract

A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types. © 2010 Macmillan Publishers Limited. All rights reserved.

Original language	English
Pages (from-to)	899-905
Journal	Nature
Volume	463
DOIs	https://doi.org/10.1038/nature08822
Publication status	Published - 18 Feb 2010

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Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., McHenry, K. T., Pinchback, R. M., Ligon, A. H., Cho, Y. J., Haery, L., Greulich, H., Reich, M., Winckler, W., Lawrence, M. S., ... Meyerson, M. (2010). The landscape of somatic copy-number alteration across human cancers. Nature, 463, 899-905. https://doi.org/10.1038/nature08822

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title = "The landscape of somatic copy-number alteration across human cancers",

abstract = "A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types. {\textcopyright} 2010 Macmillan Publishers Limited. All rights reserved.",

author = "Rameen Beroukhim and Mermel, {Craig H.} and Dale Porter and Guo Wei and Soumya Raychaudhuri and Jerry Donovan and Jordi Barretina and Boehm, {Jesse S.} and Jennifer Dobson and Mitsuyoshi Urashima and McHenry, {Kevin T.} and Pinchback, {Reid M.} and Ligon, {Azra H.} and Cho, {Yoon Jae} and Leila Haery and Heidi Greulich and Michael Reich and Wendy Winckler and Lawrence, {Michael S.} and Weir, {Barbara A.} and Tanaka, {Kumiko E.} and Chiang, {Derek Y.} and Bass, {Adam J.} and Alice Loo and Carter Hoffman and John Prensner and Ted Liefeld and Qing Gao and Derek Yecies and Sabina Signoretti and Elizabeth Maher and Kaye, {Frederic J.} and Hidefumi Sasaki and Tepper, {Joel E.} and Fletcher, {Jonathan A.} and Josep Tabernero and Jos{\'e} Baselga and Tsao, {Ming Sound} and Francesca Demichelis and Rubin, {Mark A.} and Janne, {Pasi A.} and Daly, {Mark J.} and Carmelo Nucera and Levine, {Ross L.} and Ebert, {Benjamin L.} and Stacey Gabrie and Rustgi, {Anil K.} and Antonescu, {Cristina R.} and Marc Ladanyi and Anthony Letai and Garraway, {Levi A.} and Massimo Loda and Beer, {David G.} and True, {Lawrence D.} and Aikou Okamoto and Pomeroy, {Scott L.} and Samuel Singer and Golub, {Todd R.} and Lander, {Eric S.} and Gad Getz and Sellers, {William R.} and Matthew Meyerson",

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doi = "https://doi.org/10.1038/nature08822",

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volume = "463",

pages = "899--905",

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Beroukhim, R, Mermel, CH, Porter, D, Wei, G, Raychaudhuri, S, Donovan, J, Barretina, J, Boehm, JS, Dobson, J, Urashima, M, McHenry, KT, Pinchback, RM, Ligon, AH, Cho, YJ, Haery, L, Greulich, H, Reich, M, Winckler, W, Lawrence, MS, Weir, BA, Tanaka, KE, Chiang, DY, Bass, AJ, Loo, A, Hoffman, C, Prensner, J, Liefeld, T, Gao, Q, Yecies, D, Signoretti, S, Maher, E, Kaye, FJ, Sasaki, H, Tepper, JE, Fletcher, JA, Tabernero, J, Baselga, J, Tsao, MS, Demichelis, F, Rubin, MA, Janne, PA, Daly, MJ, Nucera, C, Levine, RL, Ebert, BL, Gabrie, S, Rustgi, AK, Antonescu, CR, Ladanyi, M, Letai, A, Garraway, LA, Loda, M, Beer, DG, True, LD, Okamoto, A, Pomeroy, SL, Singer, S, Golub, TR, Lander, ES, Getz, G, Sellers, WR & Meyerson, M 2010, 'The landscape of somatic copy-number alteration across human cancers', Nature, vol. 463, pp. 899-905. https://doi.org/10.1038/nature08822

TY - JOUR

T1 - The landscape of somatic copy-number alteration across human cancers

AU - Beroukhim, Rameen

AU - Mermel, Craig H.

AU - Porter, Dale

AU - Wei, Guo

AU - Raychaudhuri, Soumya

AU - Donovan, Jerry

AU - Barretina, Jordi

AU - Boehm, Jesse S.

AU - Dobson, Jennifer

AU - Urashima, Mitsuyoshi

AU - McHenry, Kevin T.

AU - Pinchback, Reid M.

AU - Ligon, Azra H.

AU - Cho, Yoon Jae

AU - Haery, Leila

AU - Greulich, Heidi

AU - Reich, Michael

AU - Winckler, Wendy

AU - Lawrence, Michael S.

AU - Weir, Barbara A.

AU - Tanaka, Kumiko E.

AU - Chiang, Derek Y.

AU - Bass, Adam J.

AU - Loo, Alice

AU - Hoffman, Carter

AU - Prensner, John

AU - Liefeld, Ted

AU - Gao, Qing

AU - Yecies, Derek

AU - Signoretti, Sabina

AU - Maher, Elizabeth

AU - Kaye, Frederic J.

AU - Sasaki, Hidefumi

AU - Tepper, Joel E.

AU - Fletcher, Jonathan A.

AU - Tabernero, Josep

AU - Baselga, José

AU - Tsao, Ming Sound

AU - Demichelis, Francesca

AU - Rubin, Mark A.

AU - Janne, Pasi A.

AU - Daly, Mark J.

AU - Nucera, Carmelo

AU - Levine, Ross L.

AU - Ebert, Benjamin L.

AU - Gabrie, Stacey

AU - Rustgi, Anil K.

AU - Antonescu, Cristina R.

AU - Ladanyi, Marc

AU - Letai, Anthony

AU - Garraway, Levi A.

AU - Loda, Massimo

AU - Beer, David G.

AU - True, Lawrence D.

AU - Okamoto, Aikou

AU - Pomeroy, Scott L.

AU - Singer, Samuel

AU - Golub, Todd R.

AU - Lander, Eric S.

AU - Getz, Gad

AU - Sellers, William R.

AU - Meyerson, Matthew

PY - 2010/2/18

Y1 - 2010/2/18

N2 - A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types. © 2010 Macmillan Publishers Limited. All rights reserved.

AB - A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types. © 2010 Macmillan Publishers Limited. All rights reserved.

U2 - https://doi.org/10.1038/nature08822

DO - https://doi.org/10.1038/nature08822

M3 - Article

VL - 463

SP - 899

EP - 905

ER -

The landscape of somatic copy-number alteration across human cancers

Abstract

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