| Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. | |
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MedLine Citation:
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PMID: 15659501 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. PATIENTS AND METHODS: We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively. RESULTS: Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases. CONCLUSION: Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse. |
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Authors:
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Hsuan-Ying Huang; Peter B Illei; Zhiquan Zhao; Madhu Mazumdar; Andrew G Huvos; John H Healey; Leonard H Wexler; Richard Gorlick; Paul Meyers; Marc Ladanyi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 23 ISSN: 0732-183X ISO Abbreviation: J. Clin. Oncol. Publication Date: 2005 Jan |
Date Detail:
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Created Date: 2005-01-20 Completed Date: 2005-03-11 Revised Date: 2011-06-09 |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 548-58 Citation Subset: IM |
Affiliation:
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Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Bone Neoplasms / drug therapy*, genetics*, pathology Child Child, Preschool DNA Mutational Analysis Female Follow-Up Studies Genes, p16* Genes, p53* Humans In Situ Hybridization, Fluorescence Infant Male Middle Aged Neoplasm Staging Oncogene Proteins, Fusion / genetics* Prognosis Proto-Oncogene Protein c-fli-1 Sarcoma, Ewing's / drug therapy*, genetics*, pathology Sequence Deletion Survival Analysis Transcription Factors / genetics* Treatment Outcome Tumor Suppressor Protein p14ARF / genetics* |
| Chemical | |
Reg. No./Substance:
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0/EWS-FLI fusion protein; 0/Oncogene Proteins, Fusion; 0/Proto-Oncogene Protein c-fli-1; 0/Transcription Factors; 0/Tumor Suppressor Protein p14ARF |
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