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The landscape of somatic copy-number alteration across human cancers

Author

Listed:
  • Rameen Beroukhim

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    Brigham and Women’s Hospital, 75 Francis Street
    Pathology, Pediatrics, and Systems Biology, Harvard Medical School, 25 Shattuck Street)

  • Craig H. Mermel

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • 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,
    Brigham and Women’s Hospital, 75 Francis Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • Heidi Greulich

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    Brigham and Women’s Hospital, 75 Francis Street
    Pathology, Pediatrics, and Systems Biology, Harvard Medical School, 25 Shattuck Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • Kumiko E. Tanaka

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • Derek Y. Chiang

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    UNC/Lineberger Comprehensive Cancer Center, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA)

  • Adam J. Bass

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    Brigham and Women’s Hospital, 75 Francis Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • John Prensner

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • 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
    Brigham and Women’s Hospital, 75 Francis 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
    Brigham and Women’s Hospital, 75 Francis Street)

  • Mark J. Daly

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Center, Boston, Massachusetts 02114, USA)

  • 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,
    Brigham and Women’s Hospital, 75 Francis Street
    Pathology, Pediatrics, and Systems Biology, Harvard Medical School, 25 Shattuck Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street)

  • Massimo Loda

    (Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    Brigham and Women’s Hospital, 75 Francis 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA)

  • Eric S. Lander

    (Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center,
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Pathology, Pediatrics, and Systems Biology, Harvard Medical School, 25 Shattuck Street)

  • 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,
    Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street
    Pathology, Pediatrics, and Systems Biology, Harvard Medical School, 25 Shattuck Street)

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.

Suggested Citation

  • 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, 2010. "The landscape of somatic copy-number alteration across human cancers," Nature, Nature, vol. 463(7283), pages 899-905, February.
    • Handle: RePEc:nat:nature:v:463:y:2010:i:7283:d:10.1038_nature08822
    DOI: 10.1038/nature08822
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    Cited by:

    1. Yi-Yu Chen & Jing-Yu Ge & Si-Yuan Zhu & Zhi-Ming Shao & Ke-Da Yu, 2022. "Copy number amplification of ENSA promotes the progression of triple-negative breast cancer via cholesterol biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Shixiang Wang & Chen-Yi Wu & Ming-Ming He & Jia-Xin Yong & Yan-Xing Chen & Li-Mei Qian & Jin-Ling Zhang & Zhao-Lei Zeng & Rui-Hua Xu & Feng Wang & Qi Zhao, 2024. "Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Zhixing Zhong & Junchen Hou & Zhixian Yao & Lei Dong & Feng Liu & Junqiu Yue & Tiantian Wu & Junhua Zheng & Gaoliang Ouyang & Chaoyong Yang & Jia Song, 2024. "Domain generalization enables general cancer cell annotation in single-cell and spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Andrea Lopez & Denis E. Reyna & Nadege Gitego & Felix Kopp & Hua Zhou & Miguel A. Miranda-Roman & Lars Ulrik Nordstrøm & Swathi-Rao Narayanagari & Ping Chi & Eduardo Vilar & Aristotelis Tsirigos & Evr, 2022. "Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Omar Alhalabi & Jianfeng Chen & Yuxue Zhang & Yang Lu & Qi Wang & Sumankalai Ramachandran & Rebecca Slack Tidwell & Guangchun Han & Xinmiao Yan & Jieru Meng & Ruiping Wang & Anh G. Hoang & Wei-Lien Wa, 2022. "MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Martina Minoli & Thomas Cantore & Daniel Hanhart & Mirjam Kiener & Tarcisio Fedrizzi & Federico La Manna & Sofia Karkampouna & Panagiotis Chouvardas & Vera Genitsch & Antonio Rodriguez-Calero & Eva Co, 2023. "Bladder cancer organoids as a functional system to model different disease stages and therapy response," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Dan Daniel Erdmann-Pham & Sanjit Singh Batra & Timothy K. Turkalo & James Durbin & Marco Blanchette & Iwei Yeh & Hunter Shain & Boris C. Bastian & Yun S. Song & Daniel S. Rokhsar & Dirk Hockemeyer, 2023. "Tracing cancer evolution and heterogeneity using Hi-C," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
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