EWS-ERG FUSION TRANSCRIPT PRODUCED BY CHROMOSOMAL INSERTION IN A EWING SARCOMA

The EWS gene is fused in Ewing sarcoma-like tumors by a chromosomal tr anslocation to one of the four ETS-family genes: FLI1, ERG, ETV1, and E1AF. The orientation of EWS and FLI1 on chromosomes 22 and 11, respec tively, is 5' centromeric and 31 telomeric, whereas that of ERG on chr omosome 21 is the reverse. Although 10% of Ewing-family tumors express the EWS-ERG fusion transcript, there have been no reports on tumors w ith t(21;22)(q22;q12) identified by banding cytogenetics. We found the karyotype 50, XY, +8, +8, +12, +mar in all metaphase cells from a tum or. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis performed on the tumor and direct sequencing of the products identifie d the EWS-ERG fusion transcript. Subsequent two-color fluorescence in situ hybridization (FISH) analysis with EWS and ERG clones showed the fused signals on the der(21) chromosome, but no ERG signals on the chr omosome 22 homologs. Thus, our RT-PCR and FISH analyses indicated that the chromosome 22 fragment containing the 5' portion of EWS had been inverted and inserted into chromosome 21 and had fused to the 3' porti on of ERG. This subtle chromosome aberration could not be identified b y routine cytogenetics. A chromosomal inversion/insertion has also bee n described in acute leukemia with the MLL-AF10 fusion gene, and this may be a common pathway for producing fusion of reverse-oriented genes in leukemias and solid tumors. (C) 1997 Wiley-Liss, Inc.