Human Gene Set: ZHANG_TARGETS_OF_EWSR1_FLI1_FUSION


Standard name ZHANG_TARGETS_OF_EWSR1_FLI1_FUSION
Systematic name M18322
Brief description Genes up-regulated in RD-EF cells (rhabdomyosarcoma) engineered to express EWSR1-FLI1 fusion [GeneID=2130;2313] and which are also highly expressed in Ewing's famliy tumors.
Full description or abstract Tumor-specific translocations are common in tumors of mesenchymal origin. Whether the translocation determines the phenotype, or vice versa, is debatable. Ewing's family tumors (EFT) are consistently associated with an EWS-FLI1 translocation and a primitive neural phenotype. Histogenesis and classification are therefore uncertain. To test whether EWS-FLI1 fusion gene expression is responsible for the primitive neuroectodermal phenotype of EFT, we established a tetracycline-inducible EWS-FLI1 expression system in a rhabdomyosarcoma cell line RD. Cell morphology changed after EWS-FLI1 expression, resembling cultured EFT cells. Xenografts showed typical EFT features, distinct from tumors formed by parental RD. Neuron-specific microtubule gene MAPT, parasympathetic marker cholecystokinin, and epithelial marker keratin 18 were up-regulated. Conversely, myogenesis was diminished. Comparison of the up-regulated genes in RD-EF with the Ewing's signature genes identified important EWS-FLI1 downstream genes, many involved in neural crest differentiation. These results were validated by real-time reverse transcription-PCR analysis and RNA interference technology using small interfering RNA against EWS-FLI1 breakpoint. The present study shows that the neural phenotype of Ewing's tumors is attributable to the EWS-FLI1 expression and the resultant phenotype resembles developing neural crest. Such tumors have a limited neural phenotype regardless of tissue of origin. These findings challenge traditional views of histogenesis and tumor origin.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15930281   Authors: Hu-Lieskovan S,Zhang J,Wu L,Shimada H,Schofield DE,Triche TJ
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Organism Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform AFFY_HG_U95
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Version history 3.0: Renamed from ZHANG_EFT_EWSFLI1_UP

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