A novel zinc finger gene is fused to EWS in small round cell tumor

Ewing sarcoma family of tumors share recurrent translocations that fuse EWS from 22q12 to five different members of transcription factors namely FLI-1 ERG, ETV1, E1AF and FEV. Different classes of DNA binding proteins, ATF1, WT1 and CHOP are fused to EWS generating distinct tumor phenotypes: clear c ell sarcoma, desmoplastic small round cell tumor, and myxoid liposarcoma, r espectively. We have cloned a novel gene located at 22q12 fused to EWS by a submicroscopic inversion of 22q in a small round cell sarcoma showing a tr anslocation (t(1;22)(p36.1;q12), The gene, designated ZSG (Zinc finger Sarc oma Gene), is a putative Cys(2)-His(2) zinc finger protein which contains a POZ transcriptional repressor-like domain at the N-terminus. The rearrange ment involves intron 8 of EWS and exon 1 of ZSG creating a chimeric sequenc e containing the transactivation domain of EWS fused to zinc finger domain of ZSG, This product lacks the transcriptional repressor domain at the N-te rminus of ZSG, A rearrangement of the second ZSG allele was also found in t umor cells. This is the first example of an intra-chromosomal rearrangement of chromosome 22, undetectable by cytogenetics, activating EWS in soft tis sue sarcoma.