Undifferentiated small round cell sarcomas with rare EWS gene fusions: identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV fusions

J Mol Diagn. 2007 Sep;9(4):498-509. doi: 10.2353/jmoldx.2007.070053. Epub 2007 Aug 9.

Abstract

Ewing family tumors (EFTs) are prototypical primitive small round blue cell sarcomas arising in bone or extraskeletal soft tissues in children or adolescents. EFTs show fusions of EWS with a gene of the ETS family of transcription factors, either EWS-FLI1 (90 to 95%) or EWS-ERG (5 to 10%). Rare cases with fusions of EWS to other ETS family genes, such as ETV1, E1AF, and FEV, have been identified, but their clinicopathological similarity to classic EFTs remains unclear. We report four new cases of EFT-like tumors with rare EWS fusions, including two with EWS-ETV1, one with EWS-FEV, and a fourth case in which we cloned a novel EWS-SP3 fusion, the first known cancer gene fusion involving a gene of the Sp zinc finger family. Analysis of these three new cases along with data on nine previously reported cases with fusions of EWS to ETV1, E1AF, or FEV suggest a strong predilection for extraskeletal primary sites. EFT-like cases with fusions of EWS to non-ETS translocation partners are also uncommon but involve the same amino-terminal portion of EWS, which in our novel EWS-SP3 fusion is joined to the SP3 zinc-finger DNA-binding domain. As these data further support, these types of EWS fusions are associated with primitive extraskeletal small round cell sarcomas of uncertain lineage arising mainly in the pediatric population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Karyotyping
  • Male
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Small Cell / genetics
  • Sarcoma, Small Cell / pathology*
  • Transcription Factors / genetics

Substances

  • EWS-ETV1 fusion protein, human
  • EWS-FEV fusion protein, human
  • EWS-SP3 fusion protein, human
  • Oncogene Proteins, Fusion
  • Transcription Factors