title: Molecular pathogenesis of Ewing sarcoma: new therapeutic and transcriptional targets.
abstract: Approximately one-third of sarcomas contain specific translocations. Ewing sarcoma is the prototypical member of this group of sarcomas; it was the first to be recognized pathologically as a singular entity and to have its signature translocation defined cytogenetically, which led to the identification of its key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeric transcription factor. We review recent progress in selected areas of Ewing sarcoma research, including the application of genome-wide chromatin immunoprecipitation analyses, to provide a comprehensive view of the EWS-FLI1 target gene repertoire, the identification of EWS-FLI1 target genes that may also point to therapeutically targetable pathways, and data from model systems as they relate to the elusive cell of origin of Ewing sarcoma and its possible similarities to mesenchymal stem cells.
authors.affiliation: Center for Children's Cancer Research at Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. stephen.lessnick@hci.utah.edu
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology; 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; D012512:Sarcoma, Ewing / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors