Efficacy of Temozolomide Is Correlated With 1p Loss and Methylation of the Deoxyribonucleic Acid Repair Gene MGMT in Malignant Gliomas

Dai ISHII; Atsushi NATSUME; Toshihiko WAKABAYASHI; Hisashi HATANO; Yoshio ASANO; Hiroki TAKEUCHI; Shinji SHIMATO; Motokazu ITO; Masazumi FUJII; Jun YOSHIDA

doi:10.2176/nmc.47.341

Original Articles

Efficacy of Temozolomide Is Correlated With 1p Loss and Methylation of the Deoxyribonucleic Acid Repair Gene MGMT in Malignant Gliomas

Dai ISHII, Atsushi NATSUME, Toshihiko WAKABAYASHI, Hisashi HATANO, Yoshio ASANO, Hiroki TAKEUCHI, Shinji SHIMATO, Motokazu ITO, Masazumi FUJII, Jun YOSHIDA

Author information

Dai ISHII
Department of Neurosurgery, Nagoya University School of Medicine
Atsushi NATSUME
The Center for Genetic and Regenerative Medicine, Nagoya University Hospital
Toshihiko WAKABAYASHI
The Center for Genetic and Regenerative Medicine, Nagoya University Hospital
Hisashi HATANO
Department of Neurosurgery, Nagoya University School of Medicine
Yoshio ASANO
Kariya Toyota General Hospital
Hiroki TAKEUCHI
Department of Neurosurgery, Nagoya University School of Medicine
Shinji SHIMATO
Department of Neurosurgery, Nagoya University School of Medicine
Motokazu ITO
Department of Neurosurgery, Nagoya University School of Medicine
Masazumi FUJII
Department of Neurosurgery, Nagoya University School of Medicine
Jun YOSHIDA
Department of Neurosurgery, Nagoya University School of Medicine

Keywords: malignant glioma, temozolomide, molecular genetic analysis, loss of heterozygosity, O⁶-methylguanine deoxyribonucleic acid methyltransferase, deoxyribonucleic acid methylation

JOURNAL OPEN ACCESS

2007 Volume 47 Issue 8 Pages 341-350

DOI https://doi.org/10.2176/nmc.47.341

Details

Abstract

Promoter methylation of the deoxyribonucleic acid (DNA) repair gene, O⁶-methylguanine-DNA methyltransferase (MGMT), is associated with improved outcome of patients with glioblastoma multiforme and anaplastic astrocytoma treated with temozolomide (TMZ). Molecular genetic analysis of loss of heterozygosity (LOH) of 1p, 19q, or 10q, p53 mutation, and MGMT promoter methylation was performed in 44 assessable tumor specimens obtained from 46 patients with recurrent malignant gliomas, including 21 with glioblastoma multiforme, 17 with anaplastic astrocytoma, and eight with anaplastic oligoastrocytoma, which have heterogeneous features and variable histological diagnosis, to assess the correlation with the response to TMZ. LOHs of 1p and 19q, and MGMT promoter methylation showed positive correlations with the clinical response to TMZ therapy (p < 0.005, 0.05, and 0.05, respectively; Fisher’s exact test). In addition, LOH of 1p and MGMT promoter methylation were associated with longer progression-free survival (p < 0.05 and 0.05, respectively; Cox regression analysis). LOH of 1p in the heterogeneous population of malignant gliomas may be one of the important factors besides MGMT methylation that predict better outcome in patients treated with TMZ.

Corresponding author

Register with J-STAGE for free!