• Plos One · Jan 2014

    Multicenter Study

    DGKI methylation status modulates the prognostic value of MGMT in glioblastoma patients treated with combined radio-chemotherapy with temozolomide.

    • Amandine Etcheverry, Marc Aubry, Ahmed Idbaih, Elodie Vauleon, Yannick Marie, Philippe Menei, Rachel Boniface, Dominique Figarella-Branger, Lucie Karayan-Tapon, Veronique Quillien, Marc Sanson, Marie de Tayrac, Jean-Yves Delattre, and Jean Mosser.
    • CNRS, UMR 6290, Institut Génétique et Développement de Rennes, Rennes, France; Université Rennes 1, Université Européenne de Bretagne, Biosit, Faculté de Médecine, Rennes, France; Centre Hospitalier Universitaire de Rennes, Service de Génétique Moléculaire et Génomique, Rennes, France.
    • Plos One. 2014 Jan 1;9(9):e104455.

    BackgroundConsistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status.Methods399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2.ResultsThe nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram.ConclusionsOur results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.

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