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Title: Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype      
keywords:
Transcriptome or Gene expression
ID:
PRJNA102777
description:
Understanding the molecular underpinnings of cancer is of critical importance to developing targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multi-faceted cellular phenotype thus only have been identified following signaling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signaling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state. Remarkably, 14 among 24 such 'cooperation response genes' (CRGs) were found to contribute to tumor formation in gene perturbation experiments. In contrast, only one in 14 perturbations of genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain and loss-of-function mutations. Keywords: Oncogenic mutation-specific comparison Overall design: Contains 50 samples total, 10 replicates each of parental cell line YAMC, plus bleo/Neo vector control, mp53-expressing, Ras-expressing and mp53/Ras cells. Polysomal RNA from each sample was run on Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA102777
authentication:
none
authorization:
none
ID:
pmid:18500333
dateReleased:
05-25-2008
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • K99 LM009477/LM/NLM NIH HHS/United States

  • R01 GM075299-03/GM/NIGMS NIH HHS/United States

  • T32 CA009363/CA/NCI NIH HHS/United States

  • GM075299/GM/NIGMS NIH HHS/United States

  • R01 CA090663-05/CA/NCI NIH HHS/United States

  • R01 GM075299-01/GM/NIGMS NIH HHS/United States

  • R01 CA120317/CA/NCI NIH HHS/United States

  • R01 CA090663/CA/NCI NIH HHS/United States

  • R01 GM075299-02/GM/NIGMS NIH HHS/United States

  • R01 CA120317-01A1/CA/NCI NIH HHS/United States

  • R01 CA090663-04/CA/NCI NIH HHS/United States

  • R01 CA120317-02/CA/NCI NIH HHS/United States

  • K99 LM009477-01A1/LM/NLM NIH HHS/United States

  • R01 GM075299-03S1/GM/NIGMS NIH HHS/United States

  • T32 CA009363-25/CA/NCI NIH HHS/United States

  • R01 CA090663-03/CA/NCI NIH HHS/United States

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