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Quantitative analysis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas

  • Clinical Study – Patient Study
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Abstract

Methylation of the MGMT promoter is supposed to be a predictive and prognostic factor in glioblastoma. Whether MGMT promoter methylation correlates with tumor response to temozolomide in low-grade gliomas is less clear. Therefore, we analyzed MGMT promoter methylation by a quantitative methylation-specific PCR in 22 patients with histologically verified low-grade gliomas (WHO grade II) who were treated with temozolomide (TMZ) for tumor progression. Objective tumor response, toxicity, and LOH of microsatellite markers on chromosomes 1p and 19q were analyzed. Histological classification revealed ten oligodendrogliomas, seven oligoastrocytomas, and five astrocytomas. All patients were treated with TMZ 200 mg/m2 on days 1–5 in a 4 week cycle. The median progression-free survival was 32 months. Combined LOH 1p and 19q was found in 14 patients; one patient had LOH 1p alone and one patient LOH 19q alone. The LOH status could not be determined in two patients and was normal in the remaining four. LOH 1p and/or 19q correlated with longer time to progression but not with radiological response to TMZ. MGMT promoter methylation was detectable in 20 patients by conventional PCR and quantitative analysis revealed the methylation status was between 12 and 100%. The volumetric response to chemotherapy analyzed by MRI and time to progression correlated with the level of MGMT promoter methylation. Therefore, our retrospective case series suggests that quantitative methylation-specific PCR of the MGMT promoter predicts radiological response to chemotherapy with TMZ in WHO grade II gliomas.

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Authors and Affiliations

  1. Department of Medical Oncology, University Hospital Berne, Berne, 3010, Switzerland

    Adrian F. Ochsenbein & Adrian D. Schubert

  2. Institute of Pathology, University of Berne, Berne, 3010, Switzerland

    Erik Vassella

  3. Department of Neurosurgery, University Hospital of Basel, Basel, 4031, Switzerland

    Luigi Mariani

Authors
  1. Adrian F. Ochsenbein
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  2. Adrian D. Schubert
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  3. Erik Vassella
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  4. Luigi Mariani
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Corresponding author

Correspondence to Adrian F. Ochsenbein.

Additional information

Back to back submission: Erik Vassella et al. Primer extension-based quantitative polymerase chain reaction reveals consistent differences in methlyation status of the MGMT promoter in diffusely infiltrating gliomas (WHO grade II–IV) of adults.

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Ochsenbein, A.F., Schubert, A.D., Vassella, E. et al. Quantitative analysis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas. J Neurooncol 103, 343–351 (2011). https://doi.org/10.1007/s11060-010-0395-2

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  • DOI: https://doi.org/10.1007/s11060-010-0395-2

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