DOES EXPRESSION OF DIFFERENT EWS CHIMERIC TRANSCRIPTS DEFINE CLINICALLY DISTINCT RISK GROUPS OF EWING TUMOR PATIENTS

Purpose: Because of the high heterogeneity of EWS gene fusions with FL I1 and ERG genes due to variable chromosomal breakpoint locations in E wing tumors (ET) (14 different chimeric transcripts identified so far) , we evaluated the clinical impact of the expression of diverse fusion transcripts in ET patients. Patients and Methods: In a European multi center study, 147 ET were analyzed by reverse-transciptase polymerase chain reaction (RT-PCR) and the molecular data statistically compared with all clinical data available. Results: Most rumors expressed chime ric 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 1 47) or 6 (five of 147). In five cases, chimerism between EWS exon 9 an d FLI1 exons 4 and EWS exon 7 and FLI1 exon 7 or 8 was observed. Fifte en cases of EWS-ERG rearrangement were identified, In 85 of these pati ents treated in the European Cooperative Ewing Sarcoma Studies, molecu lar results were analyzed in comparison to age, sex, tumor localizatio n, tumor volume, and disease extension. No significant correlation bet ween the various fusion types and these features were observed. Relaps e-free survival (RFS) for the 31 patients with localized disease and f usion type I tended to be longer compared with the 24 patients with lo calized tumors bearing other chimeric transcripts (P = .04). (C) 1996 by American Society of Clinical Oncology. Conclusion: Results suggest a possible advantage in RFS for patients with localized disease and fu sion type I transcripts, although this will require prospective valida tion with a larger number of patients and longer follow-up periods.