ABSENCE OF DETECTABLE EWS FLI1 EXPRESSION AFTER THERAPY-INDUCED NEURAL DIFFERENTIATION IN EWING SARCOMA/

Ewing sarcoma and other peripheral primitive neuroectodermal tumors (p PNETs) display limited neural differentiation and are thought to have a neural crest origin, Greater than 95% of these tumors share common t (11;22)(q24;q12) or t(21;22) (q22;q12) chromosomal translocations lead ing to EWS/FLI1 or EWS/ERG gene fusions, respectively. The resulting c himeric oncoproteins seem to function as aberrant transcription factor s, However, whether these molecules contribute to the limited neural d ifferentiation observed in pPNETs or actually inhibit differentiation remains unclear, We report a Ewing sarcoma case from the forearm of a 10-year-old girl which expressed EWS/FLI1 fusion transcripts, The tumo r was treated with surgery, chemotherapy, and local radiation, but res idual tumor was detected within a year as a well-differentiated periph eral neural tumor lacking detectable EWS/FLI1 expression. Further stud ies suggested that the primary and residual tumors were clonally relat ed. This association between apparent therapy-induced differentiation in Ewing sarcoma and absence of detectable fusion transcripts in the r esidual tumor provides presumptive evidence that EWS/FLI1 expression m ay inhibit differentiation in tumour cells. Copyright (C) 1998 by WE. Saunders Company.