Human Gene Set: SWEET_KRAS_ONCOGENIC_SIGNATURE


Standard name SWEET_KRAS_ONCOGENIC_SIGNATURE
Systematic name M10573
Brief description Genes that contributed maximally to the GSEA score of the up-regulated gene set from the KrasLA mouse model in two human lung cancer expression data sets comparing mutant vs normal KRAS [GeneID=3845].
Full description or abstract Using advanced gene targeting methods, generating mouse models of cancer that accurately reproduce the genetic alterations present in human tumors is now relatively straightforward. The challenge is to determine to what extent such models faithfully mimic human disease with respect to the underlying molecular mechanisms that accompany tumor progression. Here we describe a method for comparing mouse models of cancer with human tumors using gene-expression profiling. We applied this method to the analysis of a model of Kras2-mediated lung cancer and found a good relationship to human lung adenocarcinoma, thereby validating the model. Furthermore, we found that whereas a gene-expression signature of KRAS2 activation was not identifiable when analyzing human tumors with known KRAS2 mutation status alone, integrating mouse and human data uncovered a gene-expression signature of KRAS2 mutation in human lung cancer. We confirmed the importance of this signature by gene-expression analysis of short hairpin RNA-mediated inhibition of oncogenic Kras2. These experiments identified both a pattern of gene expression indicative of KRAS2 mutation and potential effectors of oncogenic KRAS2 activity in human cancer. This approach provides a strategy for using genomic analysis of animal models to probe human disease.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15608639   Authors: Sweet-Cordero A,Mukherjee S,Subramanian A,You H,Roix JJ,Ladd-Acosta C,Mesirov J,Golub TR,Jacks T
Exact source Table 6S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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