[Role of MGMT and clinical applications in brain tumours].
Glioblastoma multiforme is the most common and most malignant primary brain tumour with a dismal prognosis. The advent of new chemotherapies with alkylating agents crossing the blood-brain barrier, like temozolomide, have permitted to notably ameliorate the survival of a subgroup of patients. Improved outcome was associated with epigenetic silencing of the MGMT (O6-methylguanin methyltransferase) gene by promotor methylation, thereby blocking its repair capability, thus rendering the alkylating agents more effective. This particularity can be tested by methylation specific PCR on resected tumour tissue, best on fresh frozen biopsies, and allows identification of patients more susceptible to respond favourably to the treatment.
Paus
Christophe
C
Service de neurochirurgie, Centre hospitalier universitaire vaudois(CHUV) et Université de Lausanne, Bugnon 46, 1011 Lausanne, Suisse. christophe.paus@chuv.ch
Murat
Anastasia
A
Stupp
Roger
R
Regli
Luca
L
Hegi
Monika
M
D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D020868:Gene Silencing; D018390:Gene Targeting; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
D018906:Antineoplastic Agents, Alkylating; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes