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Series GSE9199 Query DataSets for GSE9199
Status Public on May 25, 2008
Title Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Contributor(s) Land H, McMurray HR, Sampson ER, Chen S, Salzman P, Klebanov L, Yakovlev A
Citation(s) 18500333
Submission date Sep 30, 2007
Last update date Feb 11, 2019
Contact name Hartmut Land
E-mail land@urmc.rochester.edu
Organization name University of Rochester Medical Center
Department Biomedical Genetics
Street address 601 Elmwood Avenue, Box 633
City Rochester
State/province NY
ZIP/Postal code 14642
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (50)
GSM232271 YAMC_polysomal_Rep7
GSM232272 YAMC_polysomal_Rep6
GSM232273 YAMC_polysomal_Rep5
Relations
BioProject PRJNA102777

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Supplementary file Size Download File type/resource
GSE9199_RAW.tar 305.9 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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