Ewing tumor: Tumor biology and clinical applications

The Ewing tumor family includes classical Ewing's sarcoma of bone and soft tissues, peripheral primitive neuroectodermal tumors (pPNET), Askin tumor, and other less frequent variants. This group of tumors is defined hy the co nsistent presence of chromosomal translocations resulting in gene fusions b etween EWS gene and a member of the ETS family of transcription factors, ma inly FLI1 and ERG. Analogous fusions are seen in other solid developmental tumors, like desmoplastic small round cell tumor. These fusions, which are consistently present and tumor-specific, control transcription of several t arget genes, largely unknown but critical to cell proliferation and differe ntiation. Therefore. gene fusions are useful to diagnose and classify small round cell tumors, have prognostic significance, are probably useful to de tect micrometastasis and monitor minimal residual disease, and are potentia l therapeutic targets. Secondary molecular alterations, which include mutat ions of cell cycle regulatory genes, are not tumor-specific but are related to progression and may have prognostic value. The Ewing rumor family repre sents a paradigm of the application of the knowledge of biology of neoplasi a to the clinical management of patients.