Biology of EWS/ETS fusions in Ewing's family tumors

Tumor-associated chromosomal translocations lead to the formation of chimer ic fusions between the EWS gene and one of five different ETS transcription factors in Ewing's family tumors (EFTs). The resultant EWS/ETS proteins pr omote oncogenesis in a dominant fashion in model systems and are necessary for continued growth of EFT cell lines. EWS belongs to a family of genes th at encode proteins that may serve as adapters between the RNA polymerase II complex and RNA splicing factors. EWS/ETS fusions have biochemical charact eristics of aberrant transcription factors and appear to promote abnormal c ellular growth by transcriptionally modulating a network of target genes. E arly evidence suggests that EWS/ETS proteins may also impact gene expressio n through alteration in RNA processing. Elucidation of EWS/ETS target gene networks in the context of other signaling pathways will hopefully lead to biology based therapeutic strategies for EFT.