Ewing's sarcoma and peripheral primitive neuroectodermal tumors after their genetic union

The Ewing family of tumors has been defined by the presence of an EWS-ets gene rearrangement. Using molecular techniques for the visualization of this aberration, several tumors of unusual location and histology were recently identified and added to this group. Increasing experimental data suggest that EWS-ets fusions act as transforming transcription factors. Subtractive screening of transgenic fibroblasts has led to the identification of potential targets. The authentic cellular context for these aberrant gene products is still unknown and may be diverse, however. Clinical heterogeneity has stimulated a search for genetic factors that may relate to treatment response. The effect of the EWS-ets fusion transcript structure on localized disease has been recently confirmed and frequent p16 tumor suppressor alterations have been described. The presence of metastases at diagnosis as the major predictor of outcome has been assessed on a submicroscopic level by reverse transcriptase-polymerase chain reaction. Problems arising from these studies are discussed, although the biological basis for variable disease extension remains obscure.