Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin

Chul-Kee Park; Sung-Hye Park; Se-Hoon Lee; Chae-Yong Kim; Dong-Wan Kim; Sun Ha Paek; Dong Gyu Kim; Dae Seog Heo; Il Han Kim; Hee-Won Jung

doi:10.1111/j.1440-1789.2008.00998.x

Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin

Neuropathology. 2009 Aug;29(4):443-9. doi: 10.1111/j.1440-1789.2008.00998.x. Epub 2009 Jan 6.

Authors

Chul-Kee Park¹, Sung-Hye Park, Se-Hoon Lee, Chae-Yong Kim, Dong-Wan Kim, Sun Ha Paek, Dong Gyu Kim, Dae Seog Heo, Il Han Kim, Hee-Won Jung

Affiliation

¹ Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.

PMID: 19170894
DOI: 10.1111/j.1440-1789.2008.00998.x

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Brain Neoplasms / drug therapy
Brain Neoplasms / enzymology*
Brain Neoplasms / genetics
Cisplatin / administration & dosage
DNA Methylation / drug effects
DNA Methylation / physiology*
DNA Modification Methylases / genetics*
DNA Modification Methylases / metabolism*
DNA Repair Enzymes / genetics*
DNA Repair Enzymes / metabolism*
Female
Gene Expression Regulation, Neoplastic / drug effects
Glioblastoma / drug therapy*
Glioblastoma / enzymology*
Glioblastoma / genetics
Humans
Male
Middle Aged
Nimustine / administration & dosage
Predictive Value of Tests
Promoter Regions, Genetic / drug effects*
Promoter Regions, Genetic / physiology
Treatment Outcome
Tumor Suppressor Proteins / genetics*
Tumor Suppressor Proteins / metabolism*
Young Adult

Substances

Biomarkers, Tumor
Tumor Suppressor Proteins
Nimustine
DNA Modification Methylases
MGMT protein, human
DNA Repair Enzymes
Cisplatin