|
Inactivation
of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating
agents
Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF,
Vanaclocha V, Baylin SB, Herman JG
Division of Cancer Biology, Johns Hopkins Oncology Center,
Baltimore, MD 21231, USA
Background. The DNA-repair enzyme O6-methylguanine-DNA methyltransferase
(MGMT) inhibits the killing of tumor cells by alkylating agents.
MGMT activity is controlled by a promoter; methylation of the promoter silences
the gene in cancer, and the cells no longer produce MGMT.
We examined gliomas to determine whether methylation of the MGMT promoter is
related to the responsiveness of the tumor to alkylating agents.
Methods. We analyzed the MGMT promoter in tumor DNA by a methylation-specific
polymerase-chain-reaction assay. The gliomas were obtained from patients who had
been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU).
The molecular data were correlated with the clinical outcome.
Results. The MGMT promoter was methylated in gliomas from 19 of 47
patients (40 percent).
This finding was associated with regression of the tumor and prolonged overall
and disease-free survival.
It was an independent and stronger prognostic factor than age, stage, tumor
grade, or performance status.
Conclusions. Methylation of the MGMT promoter in gliomas is a useful
predictor of the responsiveness of the tumors to alkylating agents.
PMID: 11070098 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11070098&dopt=Abstract |