Ewing sarcoma has a lower rate of somatic mutations than most cancers (Brohl et al., 2014; Crompton et al., 2014; Huether et al., 2014; Lawrence et al., 2013; Tirode et al., 2014), suggesting that EWS-FLI1-driven tumors may be particularly dependent on deregulation of the epigenome. This evidence concerns the gene EWSR1 and Ewing sarcoma.