Ewing's sarcomas are characterized by recurrent chromosomal translocations 
expressing EWS-ETS fusion proteins, the most common of which is EWS-FLI.(1-5) 
EWS-FLI is an oncogenic transcription factor that regulates genes involved in 
tumorigenesis.(6,7) Because the Ewing's sarcoma cell of origin remains unknown, 
a variety of model systems have been developed to study EWS-FLI fusions,(8-14) 
and multiple microarray experiments describing potential EWS-FLI target genes 
have been reported.(8,10,11,13,15-21) Each model has potential benefits and 
drawbacks, but a large-scale comparison of these has not been reported. Herein 
we report a meta-analysis of the genes that are dysregulated by EWS-FLI in 
Ewing's sarcoma model systems. In general, EWS-FLI gain- and loss-of-function 
models in human cell types were well correlated to patient-derived tumor 
samples, while murine models were not. Using frequency analysis of dysregulated 
genes across multiple model systems, we identified a conserved "core" EWS-FLI 
transcriptional signature. This signature contained many of the genes known to 
be involved in the tumorigenic phenotype of Ewing's sarcoma, and also contained 
genes that have not been previously reported. Comparisons between the core 
EWS-FLI signature and published mesenchymal stem cell data support the recent 
assertion that mesenchymal stem cells are likely the Ewing's sarcoma precursor 
cell.(15) These results demonstrate the utility of using comparative analysis to 
validate model systems and emphasize the unique potential of this approach to 
identify both oncogenic and background cell signatures.