O-methylguanine-DNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation

We analyzed prospectively whether MGMT (O(6)-methylguanine-DNA methyltransferase) mRNA expression gains prognostic/predictive impact independent of MGMT promoter methylation in malignant glioma patients undergoing radiotherapy with concomitant and adjuvant temozolomide or temozolomide alone. As DNA-...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2011-02, Vol.6 (2), p.e17156
Main Authors: Kreth, Simone, Thon, Niklas, Eigenbrod, Sabina, Lutz, Juergen, Ledderose, Carola, Egensperger, Rupert, Tonn, Joerg C, Kretzschmar, Hans A, Hinske, Ludwig C, Kreth, Friedrich W
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating - therapeutic use
Brain Neoplasms - diagnosis
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - therapy
Chemotherapy, Adjuvant
Dacarbazine - analogs & derivatives
Dacarbazine - therapeutic use
DNA Methylation - drug effects
DNA Methylation - physiology
Drug Resistance, Neoplasm - genetics
Female
Gene Expression Regulation, Neoplastic - drug effects
Glioma - diagnosis
Glioma - genetics
Glioma - metabolism
Glioma - therapy
Humans
Male
Middle Aged
O-Methylguanine-DNA Methyltransferase - genetics
O-Methylguanine-DNA Methyltransferase - metabolism
Prognosis
Promoter Regions, Genetic - drug effects
Promoter Regions, Genetic - genetics
Radiotherapy, Adjuvant
RNA, Messenger - analysis
RNA, Messenger - genetics
RNA, Messenger - metabolism
Temozolomide
Treatment Outcome
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We analyzed prospectively whether MGMT (O(6)-methylguanine-DNA methyltransferase) mRNA expression gains prognostic/predictive impact independent of MGMT promoter methylation in malignant glioma patients undergoing radiotherapy with concomitant and adjuvant temozolomide or temozolomide alone. As DNA-methyltransferases (DNMTs) are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells, we analyzed further, whether MGMT promoter methylation is associated with upregulation of DNMT expression. ADULT PATIENTS WITH A HISTOLOGICALLY PROVEN MALIGNANT ASTROCYTOMA (GLIOBLASTOMA: N = 53, anaplastic astrocytoma: N = 10) were included. MGMT promoter methylation was determined by methylation-specific PCR (MSP) and sequencing analysis. Expression of MGMT and DNMTs mRNA were analysed by real-time qPCR. Prognostic factors were obtained from proportional hazards models. Correlation between MGMT mRNA expression and MGMT methylation status was validated using data from the Cancer Genome Atlas (TCGA) database (N = 229 glioblastomas). Low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p
ISSN:1932-6203
DOI:10.1371/journal.pone.0017156