Translocation involving a fusion of the EWS gene (22q12) and one of the partner genes is a specific marker of Ewing's sarcoma (EWS) and primitive neuroectodermal tumor (PNET).

Approximately in 85 % of all cases there is detected a fusion with FLI1 gene (11q24) from the ETS group of transcription factors. In remaining 10 - 15 % there is found a fusion with the ERG gene (21q22), a close relative of the genes ETS. As a minority there are also found another fusion partners from the ETS group of genes, such as ETV1 (7p22), E1AF(17q21) and FEV(2q36) (translocation) and ZSG(22q12) (inversion).

In this fusion, it leads to the joining of N-terminal activation domain of the gene EWS with C-terminal DNA binding domain of the gene ETS. This gives a rise to the aberrant, highly oncogenic protein which binds the target genes ETS and activates them.

Examination

The presence of the break in the EWS gene region is analyzed by FISH using EWSR1 Dual Color, Break Apart Rearrangement Probe, Vysis/Abbot (this probe does not identify the specific translocation partner). In a sample positive for rearrangement of the gene EWSR1 we observe one yellow, one red and one green signal (fig. 1A). In a negative sample we observe two yellow signals (fig. 1B).

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  Fig.1A

  EWSR1
  
  A) Nucleus positive for the EWSR1 gene breakage.

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  Fig.1B

  EWSR1
  
  B) Nucleus negative for the EWSR1 gene breakage.