EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.
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 fusio...
| Publicado en: | Journal of Clinical Oncology Vol. 16; no. 4; pp. 1248 - 1256 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Society of Clinical Oncology
Apr1998
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=88362897&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 88362897 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0732183X 20D jtl: Journal of Clinical Oncology issn: 0732183X maglogo: N pubinfo: dt: Apr1998 vid: 16 iid: 4 pid: 26892 pub: American Society of Clinical Oncology place: Alexandria, Virginia artinfo: ui: 88362897 88362897 NLM9552022 88362897 NLM9552022 88362897 ppf: 1248 ppct: 8 formats: tig: atl: EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. aug: au: de Alava, Enrique Kawai, Akira Healey, John H. Fligman, Igal Meyers, Paul A. Huvos, Andrew G. Gerald, William L. Jhanwar, Suresh C. Argani, Pedram Antonescu, Cristina R. Pardo-Mindan, F. Javier Ginsberg, Jill Womer, Richard Lawlor, Elizabeth R. Wunder, Jay Andrulis, Irene Sorensen, Poul H. B. Barr, Frederic G. Ladanyi, Marc de Alava, E affil: Clinica Universitaria de Navarra, Pamplona, Spain sug: subj: Bone Neoplasms Drug Therapy Proteins Osteosarcoma Drug Therapy Antineoplastic Agents, Combined Therapeutic Use Bone Neoplasms Male Osteosarcoma Human Bone Neoplasms Mortality Osteosarcoma Mortality Adult Multivariate Analysis Female Genes Prognosis Proteins Classification Survival Analysis Polymerase Chain Reaction Adolescence Validation Studies Comparative Studies Evaluation Research Multicenter Studies Clinical Assessment Tools Scales Adult: 19-44 years Adolescent: 13-18 years Male Female ab: 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 [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis. Conclusion: EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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