title: Promiscuous partnerships in Ewing's sarcoma.
abstract: Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing's sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing's sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing's sarcoma. However, in recent years there have been reports of rare fusions in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing's sarcoma and Ewing's-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor.
authors.affiliation: Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Sankar
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D015321:Gene Rearrangement; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics* / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C106031:EWS-FLI fusion protein; D051741:Kruppel-Like Transcription Factors; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D050814:Octamer Transcription Factor-3; D015514:Oncogene Proteins, Fusion; C412784:PATZ1 protein, human; C494173:POU5F1 protein, human; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012097:Repressor Proteins; C497121:SP3 protein, human; D051705:Sp3 Transcription Factor; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human