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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 | Matthew Meyerson
Nature | 2010

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.

Pubmed ID: 20164920 RIS Download

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Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: U54 HG003067
  • Agency: NCI NIH HHS, United States
    Id: P01CA 098101
  • Agency: NCI NIH HHS, United States
    Id: K08 CA122833-02
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007753
  • Agency: NCI NIH HHS, United States
    Id: R01 CA109038
  • Agency: NCI NIH HHS, United States
    Id: P01 CA085859
  • Agency: NCI NIH HHS, United States
    Id: K08 CA122833-03
  • Agency: NCI NIH HHS, United States
    Id: R01CA109467
  • Agency: NIAMS NIH HHS, United States
    Id: K08 AR055688-04
  • Agency: NIAMS NIH HHS, United States
    Id: K08 AR055688
  • Agency: NCI NIH HHS, United States
    Id: U24 CA126546
  • Agency: NCI NIH HHS, United States
    Id: K08CA122833
  • Agency: NIAMS NIH HHS, United States
    Id: K08 AR055688-03
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NCI NIH HHS, United States
    Id: K08 CA134931
  • Agency: NCI NIH HHS, United States
    Id: R01CA109038
  • Agency: NCI NIH HHS, United States
    Id: K08 CA122833-01A1
  • Agency: NCI NIH HHS, United States
    Id: K08 CA122833
  • Agency: NCI NIH HHS, United States
    Id: P01CA085859
  • Agency: NCI NIH HHS, United States
    Id: P01 CA098101
  • Agency: NCI NIH HHS, United States
    Id: R01 CA109467
  • Agency: NCI NIH HHS, United States
    Id: P50CA90578
  • Agency: NCI NIH HHS, United States
    Id: P50 CA090578

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BioCarta Pathways (tool)

RRID:SCR_006917

BioCarta Pathways allows users to observe how genes interact in dynamic graphical models. Online maps available within this resource depict molecular relationships from areas of active research. In an open source approach, this community-fed forum constantly integrates emerging proteomic information from the scientific community. It also catalogs and summarizes important resources providing information for over 120,000 genes from multiple species. Find both classical pathways as well as current suggestions for new pathways.

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GLAD (tool)

RRID:SCR_001284

Software for analysis of array CGH data: detection of breakpoints in genomic profiles and assignment of a status (gain, normal or loss) to each chromosomal regions identified.

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