Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin.
We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter using a methylation-specific polymerase chain reaction (MSP) in glioblastoma patients treated with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) plus cisplatin followed by radiation therapy. Forty-eight patients with interpretable MSP results were included in this study. The MGMT promoter was methylated in 26 patients (54.2%, methylated group) and unmethylated in 22 patients (45.8%, unmethylated group). Comparison of clinical outcomes between the two groups revealed that the methylation status of the MGMT gene promoter was not a prognostic factor for overall survival (P = 0.516) or a predictive factor for radiological response to ACNU plus cisplatin treatment (P = 0.529). The most noteworthy explanation for the result is that the synergistic antitumor effects of ACNU and cisplatin resulting from inactivation of MGMT by cisplatin in MGMT active tumors offset the drug resistance.
Park
Chul-Kee
CK
Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.
Park
Sung-Hye
SH
Lee
Se-Hoon
SH
Kim
Chae-Yong
CY
Kim
Dong-Wan
DW
Paek
Sun Ha
SH
Kim
Dong Gyu
DG
Heo
Dae Seog
DS
Kim
Il Han
IH
Jung
Hee-Won
HW
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015376:Nimustine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D002945:Cisplatin