Article
Nature 463, 899-905 (18 February 2010) | doi:10.1038/nature08822; Received 2 June 2009; Accepted 23 December 2009
The landscape of somatic copy-number alteration across human cancers
医学: ヒトがんの体細胞性コピー数変化の全体像
Rameen Beroukhim1,3,4,5,24, Craig H. Mermel1,3,24, Dale Porter8, Guo Wei1, Soumya Raychaudhuri1,4, Jerry Donovan8, Jordi Barretina1,3, Jesse S. Boehm1, Jennifer Dobson1,3, Mitsuyoshi Urashima9, Kevin T. Mc Henry8, Reid M. Pinchback1, Azra H. Ligon4, Yoon-Jae Cho6, Leila Haery1,3, Heidi Greulich1,3,4,5, Michael Reich1, Wendy Winckler1, Michael S. Lawrence1, Barbara A. Weir1,3, Kumiko E. Tanaka1,3, Derek Y. Chiang1,3,13, Adam J. Bass1,3,4, Alice Loo8, Carter Hoffman1,3, John Prensner1,3, Ted Liefeld1, Qing Gao1, Derek Yecies3, Sabina Signoretti3,4, Elizabeth Maher10, Frederic J. Kaye11, Hidefumi Sasaki12, Joel E. Tepper13, Jonathan A. Fletcher4, Josep Tabernero14, José Baselga14, Ming-Sound Tsao15, Francesca Demichelis16, Mark A. Rubin16, Pasi A. Janne3,4, Mark J. Daly1,17, Carmelo Nucera7, Ross L. Levine18, Benjamin L. Ebert1,4,5, Stacey Gabriel1, Anil K. Rustgi19, Cristina R. Antonescu18, Marc Ladanyi18, Anthony Letai3, Levi A. Garraway1,3, Massimo Loda3,4, David G. Beer20, Lawrence D. True21, Aikou Okamoto22, Scott L. Pomeroy6, Samuel Singer18, Todd R. Golub1,3,23, Eric S. Lander1,2,5, Gad Getz1, William R. Sellers8 & Matthew Meyerson1,3,5
- 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
- Departments of Medical Oncology, Pediatric Oncology, and Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street,
- Departments of Medicine and Pathology, Brigham and Women’s Hospital, 75 Francis Street,
- Departments of Medicine, Pathology, Pediatrics, and Systems Biology, Harvard Medical School, 25 Shattuck Street,
- Department of Neurology, Children’s Hospital Boston, 300 Longwood Avenue,
- Department of Pathology, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Boston, Massachusetts 02115, USA
- Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
- Division of Molecular Epidemiology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390-9186, USA
- Genetics Branch, Center for Cancer Research, National Cancer Institute and National Naval Medical Center, Bethesda, Maryland 20889, USA
- Department of Surgery II, Nagoya City University Medical School, Nagoya 467-8601, Japan
- Department of Genetics and Radiation Oncology, UNC/Lineberger Comprehensive Cancer Center, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA
- Medical Oncology Program, Vall d’Hebron University Hospital Research Institute, Vall d’Hebron Institute of Oncology, and Autonomous University of Barcelona, 08035 Barcelona, Spain
- Department of Pathology and Division of Applied Molecular Oncology, University Health Network, Princess Margaret Hospital and Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10065, USA
- Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Center, Boston, Massachusetts 02114, USA
- Departments of Medicine and Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
- Departments of Medicine (GI Division) and Genetics, and Abramson Cancer Center, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
- Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Ann Arbor, Michigan 48109, USA
- Department of Pathology, University of Washington Medical Center, 1959 North East Pacific Street, Seattle, Washington 98195-6100, USA
- Department of Obstetrics and Gynecology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan
- Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA
- These authors contributed equally to this work.
Correspondence to: Eric S. Lander1,2,5Gad Getz1William R. Sellers8Matthew Meyerson1,3,5 Correspondence and requests for materials should be addressed to E.S.L. (Email: lander@broadinstitute.org), G.G. (Email: gadgetz@broadinstitute.org), W.R.S. (Email: william.sellers@novartis.com) or M.M. (Email: matthew_meyerson@dfci.harvard.edu).
Abstract
腫瘍が形成される際にカギとなる役割をもつ遺伝子を発見する強力な方法は、ヒトがんにおいて頻繁に変化がみられるゲノム領域の同定である。本論文では、大部分が26の組織型に属する、3,131個のがんサンプルの体細胞性コピー数変化(SCNA)についての高解像度解析を示す。我々は、いくつかのがん種で有 意に高い頻度で変化がみられる局所的SCNA領域を、158同定した。このうちの122は、これらの領域内に位置する既知のがん標的遺伝子の存在によって 説明できないものである。アポトーシス調節因子である BCL2 ファミリーやNF-κB経路などのいくつかの遺伝子ファミリーが、これらの局所的SCNA領域中に多くみられる。 MCL1 や BCL2L1 の抗アポトーシス遺伝子周辺の増幅がみられるがん細胞の生存は、これらの遺伝子の発現に依存していることがわかった。また、個々の種類のがんで同定されたSCNAの大多数が、複数種のがんに存在することを示す。
(この訳もなんとかならんのかね!はっきり言って金銭のやりとりがあるプロの所作とは思えぬ!)
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