Balanced translocations involving band q12 of human chromosome 22 are
the most frequent recurrent translocations observed in human solid tum
ours. It has been shown recently that this region encodes EWS, a prote
in with an RNA binding homologous domain. In Ewing's sarcoma and malig
nant melanoma of soft parts, translocations of band 22q12 to chromosom
e 11 and 12 result in the fusion of EWS with the transcription factors
FLI-1 and ATF1, respectively. The present analysis of 89 Ewing's sarc
omas and related tumours show that in addition to the expected EWS-FLI
-1 fusion, the EWS gene can be fused to ERG, a transcription factor cl
osely related to FLI-1 but located on chromosome 21. The position of t
he chromosome translocation breakpoints are shown to be restricted to
introns 7-10 of the EWS gene and widely dispersed within introns 3-9 o
f the Ets-related genes. This heterogeneity generates a variety of chi
meric proteins that can be detected by immunoprecipitation. On rare oc
casions, they may be associated with a truncated EWS protein arising f
rom alternate splicing. All 13 different fusion proteins that were evi
denced contained the N-terminal domain of EWS and the Ets domain of FL
I-1 or ERG suggesting that oncogenic conversion is achieved by the lin
king of the two domains with no marked constraint on the connecting pe
ptide.