Pathogenesis of Ewing sarcoma: A review

Ewing sarcoma is a rare sarcoma of bone and soft tissue that uncommonly involve the head and neck. It is the second most common malignant tumor seen in children and young adults. It is most common observed during the second or third decade, with a male predilection. In the head and neck region, it involves skull, clavicle, maxilla, and mandible. The reported incidence of this tumor is only 1-3 cases per million of population per year and skull tumors constitute about 2% of it. The cell of origin is still unclear as there are several literature supporting both the neural crest mesenchymal progenitor/stem cells hypothesis. Ewing sarcoma is believed to be derived from recurrent EWS/E-twenty six (ETS) oncogenic fusions, which result in altered gene expression in the cell and other mechanisms. This altered gene expression is followed by the abnormal regulation in the expression of several genes and non-coding RNAs. In Ewing sarcoma, the translocation of t(11;22)(q24;q12) is considered as the primary mechanism for tumorigenesis. The tumor is characterized by the rearrangement of EWS gene on chromosome 22q12 and the fusion partners from the ETS oncogene family, chimeric transcription factor, which is responsible for the Ewing sarcoma oncogenic program. A hybrid gene is formed by the fusion of EWSR1 in 22q12 with the FLI1 gene in 11q24. EWS/FLI is the common chimeric protein that is expressed in Ewing’s sarcoma. The expression of this protein results in the growth arrest and cell death, when they are expressed in primary cell lines. The expression of these proteins in primitive cell or tumor cell causes differentiation defects resulting in oncogenesis. In this review, we have made an attempt to have an insight into the possible mechanism of pathogenesis and cell of origin of Ewing sarcoma.