Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite

Olivier Delattre and colleagues show that a Ewing sarcoma susceptibility variant at 10q21.3 influences EGR2 expression by altering the activity of an enhancer bound by EWSR1-FLI1. They further show that EGR2 knockdown inhibits growth of Ewing sarcoma cells in vitro and induces complete regression of xenografts in vivo, establishing a critical role for EGR2 in Ewing sarcomagenesis.