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	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by DeAngelis, L. M. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Epigenetic silencing of the MGMT (O⁶-methylguanine–DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents.

Methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis.

Results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups.

Conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.

Source Information

From the Laboratory of Tumor Biology and Genetics, Department of Neurosurgery (M.E.H., A.-C.D., M.-F.H., N.T.), the Departments of Radiotherapy (R.O.M.) and Neuropathology (R.C.J.), and the Multidisciplinary Oncology Center (R.S.), University Hospital Lausanne, Lausanne; the Department of Neurosurgery, University Hospital Geneva, Geneva (N.T.); the National Center of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Epalinges (M.E.H.); and the Department of Neurosurgery, Inselspital, Bern (L.M.) — all in Switzerland; the Data Center, European Organisation for Research and Treatment of Cancer, Brussels (T.G.); the Department of Neurology, University of Tübingen, Tübingen (M.W.), and the Department of Neurology, University of Regensburg, Regensburg (P.H.) — both in Germany; the Division of Neuropathology, University Hospital Rotterdam, Rotterdam (J.M.K.), and University Medical Center, Utrecht (J.E.C.B.) — both in the Netherlands; the Institute of Neurology, Medical University of Vienna, Vienna, (J.A.H.); and Princess Margaret Hospital, Toronto (W.M.), and the University of Calgary, Calgary, Alta. (J.G.C.) — both in Canada.

Address reprint requests to Dr. Hegi at the Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital (CHUV), BH19-110, 1011 Lausanne, Switzerland, or at monika.hegi{at}chuv.hospvd.ch.

Full Text of this Article

Related Letters:

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Paulino A. C., Teh B. S., Sadeh M., Seiter K., Ashby L., LaRocca R., Ryken T., Aiken R. D., Rutkowski S., Ottensmeier H., Pietsch T., Stupp R., Hegi M. E., DeAngelis L. M.
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N Engl J Med 2005; 352:2350-2353, Jun 2, 2005. Correspondence

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• Shirahata, M., Iwao-Koizumi, K., Saito, S., Ueno, N., Oda, M., Hashimoto, N., Takahashi, J. A., Kato, K. (2007). Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis. Clin. Cancer Res. 13: 7341-7356 [Abstract] [Full Text]  
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• Pyrko, P., Schonthal, A. H., Hofman, F. M., Chen, T. C., Lee, A. S. (2007). The Unfolded Protein Response Regulator GRP78/BiP as a Novel Target for Increasing Chemosensitivity in Malignant Gliomas. Cancer Res. 67: 9809-9816 [Abstract] [Full Text]  
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• Riesterer, O., Milas, L., Ang, K. K. (2007). Use of Molecular Biomarkers for Predicting the Response to Radiotherapy With or Without Chemotherapy. JCO 25: 4075-4083 [Abstract] [Full Text]  
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• Lonning, P., Knappskog, S, Staalesen, V, Chrisanthar, R, Lillehaug, J. (2007). Breast cancer prognostication and prediction in the postgenomic era. Ann Oncol 18: 1293-1306 [Abstract] [Full Text]  
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• Mikeska, T., Bock, C., El-Maarri, O., Hubner, A., Ehrentraut, D., Schramm, J., Felsberg, J., Kahl, P., Buttner, R., Pietsch, T., Waha, A. (2007). Optimization of Quantitative MGMT Promoter Methylation Analysis Using Pyrosequencing and Combined Bisulfite Restriction Analysis. J. Mol. Diagn. 9: 368-381 [Abstract] [Full Text]