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PMID: 20164920 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature ·Vol. 463 ·No. 7283 ·2010-02-18 ·Pages 899-905

Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry 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, Gabriel 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

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-kappaBeta 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.

MeSH Terms
Apoptosis/genetics Cell Line, Tumor Cell Survival/genetics DNA Copy Number Variations/genetics Gene Amplification/genetics Gene Dosage/genetics Genomics Humans Multigene Family/genetics Myeloid Cell Leukemia Sequence 1 Protein Neoplasms/classification,genetics,pathology Proto-Oncogene Proteins c-bcl-2/genetics Signal Transduction bcl-X Protein/genetics
Chemicals
BCL2L1 protein, human Myeloid Cell Leukemia Sequence 1 Protein Proto-Oncogene Proteins c-bcl-2 bcl-X Protein
Authors & Affiliations
62 authors, click to expand affiliations / ORCID
Beroukhim Rameen
Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center.
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 José
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
Garraway Levi A
Loda Massimo
Beer David G
True Lawrence D
Okamoto Aikou
Pomeroy Scott L
Singer Samuel
Golub Todd R
Lander Eric S
Getz Gad
Sellers William R
Meyerson Matthew
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature08822
Published
2010-02-18
Pages
899-905
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2826709
Subset
IM
Grants
NHGRI NIH HHS · U54 HG003067 · United States
NCI NIH HHS · P01CA 098101 · United States
NCI NIH HHS · K08 CA122833-02 · United States
NIGMS NIH HHS · T32 GM007753 · United States
NCI NIH HHS · R01 CA109038 · United States
NCI NIH HHS · P01 CA085859 · United States
NCI NIH HHS · K08 CA122833-03 · United States
NCI NIH HHS · R01CA109467 · United States
NIAMS NIH HHS · K08 AR055688-04 · United States
NIAMS NIH HHS · K08 AR055688 · United States
NCI NIH HHS · U24 CA126546 · United States
NCI NIH HHS · K08CA122833 · United States
NIAMS NIH HHS · K08 AR055688-03 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · K08 CA134931 · United States
NCI NIH HHS · R01CA109038 · United States
NCI NIH HHS · K08 CA122833-01A1 · United States
NCI NIH HHS · K08 CA122833 · United States
NCI NIH HHS · P01CA085859 · United States
NCI NIH HHS · P01 CA098101 · United States
NCI NIH HHS · R01 CA109467 · United States
NCI NIH HHS · P50CA90578 · United States
NCI NIH HHS · P50 CA090578 · United States
Databases
GEO
GSE19399
External Links
PubMed source DOI: 10.1038/nature08822 PMC Full Text View journal details
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