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. 2005 Mar 10;352(10):997-1003.
doi: 10.1056/NEJMoa043331.

MGMT gene silencing and benefit from temozolomide in glioblastoma

Monika E Hegi  1 , Annie-Claire Diserens, Thierry Gorlia, Marie-France Hamou, Nicolas de Tribolet, Michael Weller, Johan M Kros, Johannes A Hainfellner, Warren Mason, Luigi Mariani, Jacoline E C Bromberg, Peter Hau, René O Mirimanoff, J Gregory Cairncross, Robert C Janzer, Roger Stupp
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Free article

MGMT gene silencing and benefit from temozolomide in glioblastoma

Monika E Hegi et al. N Engl J Med. .
Free article

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.

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Comment in

  • Chemotherapy for brain tumors--a new beginning.
    DeAngelis LM. DeAngelis LM. N Engl J Med. 2005 Mar 10;352(10):1036-8. doi: 10.1056/NEJMe058010. N Engl J Med. 2005. PMID: 15758016 No abstract available.
  • Treatment of brain tumors.
    Aiken RD. Aiken RD. N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3. N Engl J Med. 2005. PMID: 15938011 No abstract available.
  • Treatment of brain tumors.
    Seiter K. Seiter K. N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3. N Engl J Med. 2005. PMID: 15938012 No abstract available.

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