Molecular pathogenesis of Ewing sarcoma: new therapeutic and transcriptional targets

Annu Rev Pathol. 2012;7:145-59. doi: 10.1146/annurev-pathol-011110-130237. Epub 2011 Sep 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Neoplasms / etiology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesenchymal Stem Cells / pathology
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / metabolism
  • RNA-Binding Protein EWS / genetics
  • RNA-Binding Protein EWS / metabolism
  • Sarcoma, Ewing / etiology
  • Sarcoma, Ewing / metabolism*
  • Sarcoma, Ewing / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Translocation, Genetic

Substances

  • EWS-FLI fusion protein
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • Transcription Factors