Human Gene Set: MCMURRAY_TP53_HRAS_COOPERATION_RESPONSE_DN

For the Mouse gene set with the same name, see MCMURRAY_TP53_HRAS_COOPERATION_RESPONSE_DN

Standard name MCMURRAY_TP53_HRAS_COOPERATION_RESPONSE_DN
Systematic name M9325
Brief description Down-regulated 'cooperation response genes': responded synergystically to the combination of mutant TP53 and HRAS [GeneID=7157;3265] in YAMC cells (colon).
Full description or abstract Understanding the molecular underpinnings of cancer is of critical importance to the development of 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 multifaceted cellular phenotype have therefore only been identified after signalling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signalling 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 of murine and human colon cells. Notably, 14 out of 24 'cooperation response genes' were found to contribute to tumour formation in gene perturbation experiments. In contrast, only 1 in 14 perturbations of the 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18500333   Authors: McMurray HR,Sampson ER,Compitello G,Kinsey C,Newman L,Smith B,Chen SR,Klebanov L,Salzman P,Yakovlev A,Land H
Exact source Table 1S: mp53/Ras vs. YAMC, norm Data < 1
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Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 AFFY_Mouse430
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Version history 3.0: First introduced

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