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 recurrently 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 transcription factor which may normally be regulated by cAMP. ATF-1 has not previously been implicated in oncogenesis. EWS was first identified as forming a hybrid transcript in Ewing's sarcoma, which links its N-terminal domain to the DNA binding domain of the FLI-1 gene. Thus the oncogenic conversion of EWS follows a common scheme of activation, exchanging its putative RNA binding domain with different DNA binding domains that appear to be tumour-specific.
Zucman
J
J
Laboratory de Tumour Genetics, INSERM CJF 9201, Institut Curie, Paris, France.
Delattre
O
O
Desmaze
C
C
Epstein
A L
AL
Stenman
G
G
Speleman
F
F
Fletchers
C D
CD
Aurias
A
A
Thomas
G
G
D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D015321:Gene Rearrangement; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; C111598:EWS-ATF1 fusion protein, human; D009838:Oligodeoxyribonucleotides; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors