Ewing's sarcoma is a solid tumor of the bone that primarily occurs in children 
and young adults. Most cases harbor the (11;22) (q24;q12) chromosomal 
translocation that encodes the EWS/FLI oncoprotein. EWS/FLI is an aberrant 
ETS-type transcription factor that dysregulates a number of genes important in 
the development of Ewing's sarcoma. Because EWS/FLI is the key oncoprotein in 
this tumor and ETS proteins are often dysregulated in various human cancers, 
Ewing's sarcoma serves as a useful paradigm for ETS-mediated oncogenesis. We 
recently showed that EWS/FLI interacts with GGAA-microsatellites to regulate 
some of its target genes, including NR0B1, an EWS/FLI-regulated gene that is 
required for the oncogenic phenotype of Ewing's sarcoma. While microsatellites 
typically have no ascribed function, and are sometimes considered "junk" DNA, 
our findings provide a unique role for microsatellites in cancer development. 
Furthermore, these findings may indicate a novel mechanism for normal ETS 
protein function as well. Finally, it is tempting to speculate that 
microsatellite polymorphisms may confer differences in susceptibility to Ewing's 
sarcoma, both between individuals and between populations, and other diseases 
mediated by ETS transcription factors. The observation of microsatellites as 
transcriptional response elements for EWS/FLI suggest that these elements may 
not be "junk" after all.