Approximately one-third of sarcomas contain specific translocations. Ewing 
sarcoma is the prototypical member of this group of sarcomas; it was the first 
to be recognized pathologically as a singular entity and to have its signature 
translocation defined cytogenetically, which led to the identification of its 
key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, 
chimeric transcription factor. We review recent progress in selected areas of 
Ewing sarcoma research, including the application of genome-wide chromatin 
immunoprecipitation analyses, to provide a comprehensive view of the EWS-FLI1 
target gene repertoire, the identification of EWS-FLI1 target genes that may 
also point to therapeutically targetable pathways, and data from model systems 
as they relate to the elusive cell of origin of Ewing sarcoma and its possible 
similarities to mesenchymal stem cells.