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An EWS / ERG fusion with a truncated N‐terminal domain of EWS in a Ewing's tumor
Author(s) -
Peter Martine,
Mugneret Francine,
Aurias Alain,
Thomas Gilles,
Magdelenat Henri,
Delattre Olivier
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960729)67:3<339::aid-ijc6>3.0.co;2-s
Subject(s) - exon , fusion protein , fusion gene , breakpoint , fusion transcript , biology , gene , microbiology and biotechnology , genetics , chromosomal translocation , recombinant dna
As a result of chromosome translocations, the EWS gene is fused to a variety of transcription factors in human solid tumors. Up to now, gene fusions of EWS with 6 different partners have been described. In all fusions presently reported the entire N‐terminal domain of EWS (NTD‐EWS) composed of 265 amino acids encoded by the first 7 exons of EWS was always included in the chimeric proteins, suggesting that the integrity of this domain was mandatory for the oncogenic property of the fusion proteins. We report the molecular characterization of a Ewing tumor demonstrating a reciprocal t(21;22)(q22;q12) translocation. No EWS/ERG fusion transcript could be detected with previously reported RT‐PCR primers. However, Southern‐blot experiments demonstrated that the EWS gene was disrupted within a 2‐kb PstI genomic fragment including exon 7. PCR amplification and sequence of the translocation junction fragments indicated that the breakpoint was localized within exon 7 of EWS . The resulting fusion gene encoded a chimeric protein in which a truncated NTD‐EWS was linked, in frame, to the ETS DNA‐binding domain of ERG. This observation indicates that, to avoid false negative results, RT‐PCR‐based diagnosis of tumors with EWS fusion transcripts should now include the search for such rare variants. It also suggests that the amino‐terminal portion of the NTD‐EWS, but not its carboxy terminal part, might be fundamental for the oncogenicity of the chimeric proteins. © 1996 Wiley‐Liss, Inc.