Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV

J Mol Diagn. 2007 Sep;9(4):459-63. doi: 10.2353/jmoldx.2007.070009. Epub 2007 Jul 9.


Ewing family tumors are molecularly characterized by expression of chimeric transcripts generated by specific chromosomal translocations, most commonly involving fusion of the EWS gene to a member of the ETS family of transcription factors (including FLI1, ERG, ETV1, E1AF, and FEV). Approximately 85% of reported cases of Ewing sarcoma bear an EWS-FLI1 fusion. In rare cases, FUS can substitute for EWS, with translocation t(16;21)(p11;q24) producing a FUS-ERG fusion with no EWS rearrangement. We report a case of Ewing sarcoma, presenting as a pathological fracture of the distal clavicle in a 33-year-old male, in which cytogenetic analysis revealed a single t(2;16)(q35;p11) balanced translocation. Fluorescence in situ hybridization using a commercially available diagnostic probe was negative for an EWS gene rearrangement; instead, break-apart fluorescence in situ hybridization probes for FUS and FEV were positive for a translocation involving these genes. Cloning and sequencing of the breakpoint region demonstrated an in-frame fusion of FUS to FEV. In conclusion, this represents the first reported case of Ewing family tumors demonstrating a variant translocation involving FUS and FEV and highlights the need to consider alternative permutations of fusion partners for molecular diagnosis of sarcomas.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Chromosomes, Human, Pair 16 / genetics*
  • Chromosomes, Human, Pair 2 / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Metaphase
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / genetics*
  • Sarcoma, Ewing / genetics*
  • Sarcoma, Ewing / pathology
  • Sequence Analysis, DNA
  • Translocation, Genetic / genetics*


  • EWS-FEV fusion protein, human
  • EWS-FUS protein, human
  • Oncogene Proteins, Fusion