With these highly recurrent patterns, exquisitely specific requirements are present for which fusions and which family members are transforming (i.e., there is no reported PAX4-FOXA2 as a transforming fusion in RMS, and there is no reported FOXO1-FLI in ES): why are the mechanisms that we have studied as a community so general, categorically? The gene discussed is FOXO1; the disease is Ewing sarcoma.