EWS AND ATF-1 GENE FUSION INDUCED BY T(12-22) TRANSLOCATION IN MALIGNANT-MELANOMA OF SOFT PARTS

The genes involved in the t(12;22)(q13;q12) translocation found recurr ently in malignant melanoma of soft parts have been characterized and shown to form, in four cases studied, hybrid transcripts. The deduced chimaeric protein encoded by the der(22) chromosome consists of the N- terminal domain of EWS linked to the bZIP domain of ATF-1, a transcrip tion factor which may normally be regulated by cAMP. ATF-1 has not pre viously been implicated in oncogenesis. EWS was first identified as fo rming a hybrid transcript in Ewing's sarcoma, which links its N-termin al domain to the DNA binding domain of the FLI-1 gene. Thus the oncoge nic conversion of EWS follows a common scheme of activation, exchangin g its putative RNA binding domain with different DNA binding domains t hat appear to be tumour-specific.