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Ewing’s sarcoma (EwS) is the second most common cancer that affects bone in children and adolescents. EwS is an aggressive malignancy with a projected overall survival of 70% for the low risk localized and 30% for the metastatic tumors. EwS is genetically described by its unique translocation that fuses FET family genes with the ETS family genes encoding transcription factors. The most frequent molecular event in over 90% of EwS cases is the translocation between EWSR1–FLI1. Additional events, ingincluding  TP53 , mutations, and  CDKN2A  deletions, have been reported but in low incidences. Hitherto, new research on EwS molecular processes is needed to lead to early diagnosis, disease monitoring, treatment development, improve patients’ survival, and quality of life. In this review, we outline the presently available information on the genetics underlying EwS carcinogenesis, investigate the existing understanding of the genetics underpinning EwS, and discuss the future directions for research on EwS.

Genetic alterations in Ewing’s sarcoma: What do we know so far?