MGMT Promoter Methylation Is Prognostic but Not Predictive for Outcome to Adjuvant PCV Chemotherapy in Anaplastic Oligodendroglial Tumors: A Report From EORTC Brain Tumor Group Study 26951

Autor: Marc Sanson, Winand N.M. Dinjens, Martin J B Taphoorn, Cathleen R. van der Lee-Haarloo, Judith W. M. Jeuken, Martin J. van den Bent, Marc Frenay, Ahmed Ibdaih, Alba A. Brandes, Hendrikus J. Dubbink, Johan M. Kros, Thierry Gorlia, Denis Lacombe, Monika E. Hegi
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Cancer Research
Pathology
Methyltransferase
Time Factors
Kaplan-Meier Estimate
Procarbazine
Polymerase Chain Reaction
0302 clinical medicine
Lomustine
Risk Factors
Antineoplastic Combined Chemotherapy Protocols
Promoter Regions
Genetic
DNA Modification Methylases
Brain Neoplasms
Methylation
Middle Aged
3. Good health
Europe
Gene Expression Regulation
Neoplastic
Treatment Outcome
Oncology
Chemotherapy
Adjuvant
Chromosomes
Human
Pair 1
Vincristine
030220 oncology & carcinogenesis
DNA methylation
Chromosome Deletion
medicine.drug
medicine.medical_specialty
Oligodendroglioma
Astrocytoma
Risk Assessment
Disease-Free Survival
03 medical and health sciences
Original Reports
medicine
Humans
neoplasms
Proportional Hazards Models
Temozolomide
business.industry
Tumor Suppressor Proteins
Cancer
DNA Methylation
medicine.disease
digestive system diseases
DNA Repair Enzymes
Cancer research
CpG Islands
business
Chromosomes
Human
Pair 19
030217 neurology & neurosurgery
Popis: Purpose O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT). Patients and Methods In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification. Results In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed. Conclusion In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma.
Databáze: OpenAIRE
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