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. Mc Henry, 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 Gabriel, 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 () and Matthew Meyerson ()
Additional contact information
Rameen Beroukhim: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Craig H. Mermel: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Dale Porter: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Guo Wei: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Soumya Raychaudhuri: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Jerry Donovan: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Jordi Barretina: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Jesse S. Boehm: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Jennifer Dobson: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Mitsuyoshi Urashima: Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan
Kevin T. Mc Henry: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Reid M. Pinchback: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Azra H. Ligon: Brigham and Women’s Hospital, 75 Francis Street
Yoon-Jae Cho: Children’s Hospital Boston, 300 Longwood Avenue
Leila Haery: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Heidi Greulich: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Michael Reich: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Wendy Winckler: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Michael S. Lawrence: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Barbara A. Weir: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Kumiko E. Tanaka: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Derek Y. Chiang: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Adam J. Bass: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Alice Loo: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Carter Hoffman: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
John Prensner: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Ted Liefeld: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Qing Gao: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Derek Yecies: Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
Sabina Signoretti: Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
Elizabeth Maher: UT Southwestern Medical Center, Dallas, Texas 75390-9186, USA
Frederic J. Kaye: Genetics Branch, Center for Cancer Research, National Cancer Institute and National Naval Medical Center, Bethesda, Maryland 20889, USA
Hidefumi Sasaki: Nagoya City University Medical School
Joel E. Tepper: UNC/Lineberger Comprehensive Cancer Center, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
Jonathan A. Fletcher: Brigham and Women’s Hospital, 75 Francis Street
Josep Tabernero: Medical Oncology Program, Vall d’Hebron University Hospital Research Institute, Vall d’Hebron Institute of Oncology, and Autonomous University of Barcelona
José Baselga: Medical Oncology Program, Vall d’Hebron University Hospital Research Institute, Vall d’Hebron Institute of Oncology, and Autonomous University of Barcelona
Ming-Sound Tsao: University Health Network, Princess Margaret Hospital and Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
Francesca Demichelis: Weill Cornell Medical College, New York, New York 10065, USA
Mark A. Rubin: Weill Cornell Medical College, New York, New York 10065, USA
Pasi A. Janne: Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
Mark J. Daly: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Carmelo Nucera: Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Boston, Massachusetts 02115, USA
Ross L. Levine: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
Benjamin L. Ebert: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Stacey Gabriel: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Anil K. Rustgi: and Abramson Cancer Center, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
Cristina R. Antonescu: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
Marc Ladanyi: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
Anthony Letai: Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
Levi A. Garraway: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Massimo Loda: Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
David G. Beer: Section of Thoracic Surgery, University of Michigan, Ann Arbor, Ann Arbor, Michigan 48109, USA
Lawrence D. True: University of Washington Medical Center, 1959 North East Pacific Street, Seattle, Washington 98195-6100, USA
Aikou Okamoto: Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan
Scott L. Pomeroy: Children’s Hospital Boston, 300 Longwood Avenue
Samuel Singer: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
Todd R. Golub: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Eric S. Lander: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
Gad Getz: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
William R. Sellers: Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Matthew Meyerson: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,

Nature, 2010, vol. 463, issue 7283, 899-905

Abstract: 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-κΒ 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.

Date: 2010
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DOI: 10.1038/nature08822

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