PMID- 15758010
OWN - NLM
STAT- MEDLINE
DCOM- 20050315
LR  - 20221222
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 352
IP  - 10
DP  - 2005 Mar 10
TI  - MGMT gene silencing and benefit from temozolomide in glioblastoma.
PG  - 997-1003
AB  - 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.
CI  - Copyright 2005 Massachusetts Medical Society.
FAU - Hegi, Monika E
AU  - Hegi ME
AD  - Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University 
      Hospital Lausanne, Lausanne, Switzerland. monika.hegi@chuv.hospvd.ch
FAU - Diserens, Annie-Claire
AU  - Diserens AC
FAU - Gorlia, Thierry
AU  - Gorlia T
FAU - Hamou, Marie-France
AU  - Hamou MF
FAU - de Tribolet, Nicolas
AU  - de Tribolet N
FAU - Weller, Michael
AU  - Weller M
FAU - Kros, Johan M
AU  - Kros JM
FAU - Hainfellner, Johannes A
AU  - Hainfellner JA
FAU - Mason, Warren
AU  - Mason W
FAU - Mariani, Luigi
AU  - Mariani L
FAU - Bromberg, Jacoline E C
AU  - Bromberg JE
FAU - Hau, Peter
AU  - Hau P
FAU - Mirimanoff, Rene O
AU  - Mirimanoff RO
FAU - Cairncross, J Gregory
AU  - Cairncross JG
FAU - Janzer, Robert C
AU  - Janzer RC
FAU - Stupp, Roger
AU  - Stupp R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 2.1.1.63 (O(6)-Methylguanine-DNA Methyltransferase)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
CIN - N Engl J Med. 2005 Mar 10;352(10):1036-8. PMID: 15758016
CIN - N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3. PMID: 15938011
CIN - N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3. PMID: 15938012
MH  - Antineoplastic Agents, Alkylating/*therapeutic use
MH  - Brain Neoplasms/drug therapy/*genetics/mortality/radiotherapy
MH  - Chemotherapy, Adjuvant
MH  - *DNA Methylation
MH  - Dacarbazine/*analogs & derivatives/*therapeutic use
MH  - Disease-Free Survival
MH  - *Gene Silencing
MH  - Glioblastoma/drug therapy/*genetics/mortality/radiotherapy
MH  - Humans
MH  - O(6)-Methylguanine-DNA Methyltransferase/*genetics
MH  - Polymerase Chain Reaction
MH  - Promoter Regions, Genetic
MH  - Randomized Controlled Trials as Topic
MH  - Survival Analysis
MH  - Temozolomide
EDAT- 2005/03/11 09:00
MHDA- 2005/03/16 09:00
CRDT- 2005/03/11 09:00
PHST- 2005/03/11 09:00 [pubmed]
PHST- 2005/03/16 09:00 [medline]
PHST- 2005/03/11 09:00 [entrez]
AID - 352/10/997 [pii]
AID - 10.1056/NEJMoa043331 [doi]
PST - ppublish
SO  - N Engl J Med. 2005 Mar 10;352(10):997-1003. doi: 10.1056/NEJMoa043331.