domingo, 8 de abril de 2012

PAX3/FOXO1 Fusion Gene Status Is the Key Progno... [J Clin Oncol. 2012] - PubMed - NCBI

PAX3/FOXO1 Fusion Gene Status Is the Key Progno... [J Clin Oncol. 2012] - PubMed - NCBI

J Clin Oncol. 2012 Mar 26. [Epub ahead of print]

PAX3/FOXO1 Fusion Gene Status Is the Key Prognostic Molecular Marker in Rhabdomyosarcoma and Significantly Improves Current Risk Stratification.


Edoardo Missiaglia, Pratyaksha Wirapati, and Mauro Delorenzi, Swiss Institute of Bioinformatics, Lausanne, Switzerland; Edoardo Missiaglia, Khin Thway, and Janet Shipley, The Institute of Cancer Research, Sutton, Surrey; Dan Williamson, Northern Institute for Cancer Research, Newcastle upon Tyne; Julia Chisholm and Khin Thway, Royal Marsden National Health Service Foundation Trust, Sutton; Kathy Pritchard-Jones, University College London Institute of Child Health, London, United Kingdom; Gaëlle Pierron, Olivier Delattre, and Jean-Paul Concordet, Institut Curie; Fabien Petel, Ligue Nationale Contre le Cancer, Paris; Odile Oberlin, Institut Gustave Roussy, Villejuif, France; and Mauro Delorenzi, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.


PURPOSETo improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data. PATIENTS AND METHODSTwo independent data sets of gene-expression profiling for 124 and 101 patients with RMS were used to derive prognostic gene signatures by using a meta-analysis. These and a previously published metagene signature were evaluated by using cross validation analyses. A combined clinical and molecular risk-stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was derived from 287 patients with RMS and evaluated.ResultsWe showed that our prognostic gene-expression signature and the one previously published performed well with reproducible and significant effects. However, their effect was reduced when cross validated or tested in independent data and did not add new prognostic information over the fusion gene status, which is simpler to assay. Among nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive patients. Furthermore, a new clinicomolecular risk score that incorporated fusion gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in performance over the current risk-stratification scheme. CONCLUSIONGene signatures can improve current stratification of patients with RMS but will require complex assays to be developed and extensive validation before clinical application. A significant majority of their prognostic value was encapsulated by the fusion gene status. A continuous risk score derived from the combination of clinical parameters with the presence or absence of PAX3/FOXO1 represents a robust approach to improving current risk-adapted therapy for RMS.
[PubMed - as supplied by publisher]

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