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 by the consistent presence of chromosomal translocations resulting in gene fusions between EWS gene and a member of the ETS family of transcription factors, mainly 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 target genes, largely unknown but critical to cell proliferation and differentiation. Therefore, gene fusions are useful to diagnose and classify small round cell tumors, have prognostic significance, are probably useful to detect micrometastasis and monitor minimal residual disease, and are potential therapeutic targets. Secondary molecular alterations, which include mutations of cell cycle regulatory genes, are not tumor-specific but are related to progression and may have prognostic value. The Ewing tumor family represents a paradigm of the application of the knowledge of biology of neoplasia to the clinical management of patients.