EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

作者：E de Alava, Akira Kawai, John H. Healey, I Fligman, Paul A. Meyers, Andrew G. Huvos, William L. Gerald, S.C. Jhanwar, Pedram Argani, Cristina R. Antonescu, F. J. Pardo-Mindán, Jill P. Ginsberg, Richard B. Womer, Elizabeth R. Lawlor, Jay S. Wunder, Irene L. Andrulis, P H Sorensen, Frederic G. Barr, Marc Ladanyi · 发表于：Journal of Clinical Oncology · 年份：1998 · DOI：10.1200/jco.1998.16.4.1248 · 被引用次数：528 · 研究领域：Sarcoma Diagnosis and Treatment、Cardiac tumors and thrombi、Chronic Myeloid Leukemia Treatments

PURPOSE: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance. PATIENTS AND METHODS: We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage. RESULTS: Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk...