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- Title
Prognostic impact of INK4A deletion in Ewing sarcoma.
- Authors
Wei, Guo; Antonescu, Cristina R.; de Alava, Enrique; Leung, Denis; Huvos, Andrew G.; Meyers, Paul A.; Healey, John H.; Ladanyi, Marc; Wei, G; Antonescu, C R; de Alava, E; Leung, D; Huvos, A G; Meyers, P A; Healey, J H; Ladanyi, M
- Abstract
<bold>Background: </bold>The primary genetic alteration in > 95% of Ewing sarcomas (ES) is a specific fusion of EWS with FLI1 or ERG. Secondary genetic alterations possibly involved in progression of ES are not well understood. A recent study found loss of the negative cell cycle regulator gene INK4A in 8 of 27 ES samples (30%). To confirm these findings and evaluate their prognostic significance, the authors studied INK4A deletion in 41 ES samples from 39 patients.<bold>Methods: </bold>Using Southern blot analysis with an INK4A p16 cDNA probe, the intensity of the INK4A bands in ES DNA samples was normalized to that of a control probe and compared with nondeleted control DNA; > 50% signal reduction was scored as evidence of deletion. All ES tumor DNA samples previously were confirmed to have EWS rearrangements on the same Southern blots, using a cDNA probe spanning the EWS breakpoint region.<bold>Results: </bold>Tumors from 7 patients (18%) showed INK4A deletion independent of disease stage (localized or metastatic) or sample source (primary tumor or metastasis). INK4A was a strong negative factor for disease specific survival in univariate analysis (P = 0.001) and in multivariate analysis including stage (relative risk = 6; P = 0.001).<bold>Conclusions: </bold>INK4A deletions appear to be the most frequent secondary molecular genetic alteration found to date in ES. Their possible clinical usefulness in identifying a subset of ES patients with poor prognosis merits systematic prospective analysis. [See related article on pages 783-92.]
- Publication
Cancer (0008543X), 2000, Vol 89, Issue 4, p793
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/1097-0142(20000815)89:4<793::AID-CNCR11>3.0.CO;2-M