title: Combinatorial generation of variable fusion proteins in the Ewing family of tumours.
abstract: Balanced translocations involving band q12 of human chromosome 22 are the most frequent recurrent translocations observed in human solid tumours. It has been shown recently that this region encodes EWS, a protein with an RNA binding homologous domain. In Ewing's sarcoma and malignant melanoma of soft parts, translocations of band 22q12 to chromosome 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 sarcomas 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 closely related to FLI-1 but located on chromosome 21. The position of the chromosome translocation breakpoints are shown to be restricted to introns 7-10 of the EWS gene and widely dispersed within introns 3-9 of the Ets-related genes. This heterogeneity generates a variety of chimeric proteins that can be detected by immuno-precipitation. On rare occasions, they may be associated with a truncated EWS protein arising from alternate splicing. All 13 different fusion proteins that were evidenced contained the N-terminal domain of EWS and the Ets domain of FLI-1 or ERG suggesting that oncogenic conversion is achieved by the linking of the two domains with no marked constraint on the connecting peptide.
authors.affiliation: Laboratoire de Génétique des Tumerurs, INSERM CJF 9201, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Zucman
authors.forename: T
authors.initials: T
authors.lastname: Melot
authors.forename: C
authors.initials: C
authors.lastname: Desmaze
authors.forename: J
authors.initials: J
authors.lastname: Ghysdael
authors.forename: B
authors.initials: B
authors.lastname: Plougastel
authors.forename: M
authors.initials: M
authors.lastname: Peter
authors.forename: J M
authors.initials: JM
authors.lastname: Zucker
authors.forename: T J
authors.initials: TJ
authors.lastname: Triche
authors.forename: D
authors.initials: D
authors.lastname: Sheer
authors.forename: C
authors.initials: C
authors.lastname: Turc-Carel
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D002891:Chromosomes, Human, Pair 21; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors