title: Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients?
abstract: OBJECTIVE
  Because of the high heterogeneity of EWS gene fusions with FLI1 and ERG genes due to variable chromosomal breakpoint locations in Ewing tumors (ET) (14 different chimeric transcripts identified so far), we evaluated the clinical impact of the expression of diverse fusion transcripts in ET patients.
  
  
  METHODS
  In a European multicenter study, 147 ET were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and the molecular data statistically compared with all clinical data available.
  
  
  RESULTS
  Most tumors expressed chimeric transcripts with fusion of EWS exon 7 to FLI1 exon 6 (75 of 147) (type I) or five (39 of 147) and EWS exon 10 to FLI1 exon 5 (eight of 147) or 6 (five of 147). In five cases, chimerism between EWS exon 9 and FLI1 exons 4 and EWS exon 7 and FLI1 exon 7 or 8 was observed. Fifteen cases of EWS-ERG rearrangement were identified. In 85 of these patients treated in the European Cooperative Ewing Sarcoma Studies, molecular results were analyzed in comparison to age, sex, tumor localization, tumor volume, and disease extension. No significant correlation between the various fusion types and these features were observed. Relapse-free survival (RFS) for the 31 patients with localized disease and fusion type I tended to be longer compared with the 24 patients with localized tumors bearing other chimeric transcripts (P = .04).
  
  
  CONCLUSIONS
  Results suggest a possible advantage in PFS for patients with localized disease and fusion type I transcripts, although this will require prospective validation with a larger number of patients and longer follow-up periods.
authors.affiliation: Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Zoubek
authors.forename: B
authors.initials: B
authors.lastname: Dockhorn-Dworniczak
authors.forename: O
authors.initials: O
authors.lastname: Delattre
authors.forename: H
authors.initials: H
authors.lastname: Christiansen
authors.forename: F
authors.initials: F
authors.lastname: Niggli
authors.forename: I
authors.initials: I
authors.lastname: Gatterer-Menz
authors.forename: T L
authors.initials: TL
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Jürgens
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: H
authors.initials: H
authors.lastname: Kovar
mesh_terms: D000293:Adolescent; D001859:Bone Neoplasms / Q000737:chemistry / Q000235:genetics*; D002648:Child; D005060:Europe; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D012194:RNA-Directed DNA Polymerase; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012306:Risk; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D011993:Recombinant Fusion Proteins; D012194:RNA-Directed DNA Polymerase