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The methylation of a panel of genes differentiates low-grade from high-grade gliomas

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Tumor Biology

Abstract

Epigenetic changes play an important role in the pathogenesis of gliomas and have the potential to become clinically useful biomarkers. The aim of this study was the evaluation of the profile of promoter methylation of 13 genes selected based on their anticipated diagnostic and/or prognostic value. Methylation-specific PCR (MSP) was used to assess the methylation status of MGMT, ERCC1, hMLH1, ATM, CDKN2B (p15INK4B), p14ARF, CDKN2A (p16INK4A), RASSF1A, RUNX3, GATA6, NDRG2, PTEN, and RARβ in a subset of 95 gliomas of different grades. Additionally, the methylation status of MGMT and NDRG2 was analyzed using pyrosequencing (PSQ). The results revealed that the methylation index of individual glioma patients correlates with World Health Organization (WHO) tumor grade and patient’s age. RASSF1A, RUNX3, GATA6, and MGMT were most frequently methylated, whereas the INK4B-ARF-INK4A locus, PTEN, RARβ, and ATM were methylated to a lesser extent. ERCC1, hMLH1, and NDRG2 were unmethylated. RUNX3 methylation correlated with WHO tumor grade and patient’s age. PSQ confirmed significantly higher methylation levels of MGMT and NDRG2 as compared with normal, non-cancerous brain tissue. To conclude, DNA methylation of a whole panel of selected genes can serve as a tool for glioma aggressiveness prediction.

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Acknowledgments

This study was supported by the National Science Centre of Poland grant no. N N405683240 and a scholarship support for Ph.D. students specializing in majors strategic for Greater Poland’s development, Sub-measure 8.2.2 Human Capital Operational Programme, co-financed by the European Union under the European Social Fund.

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Authors and Affiliations

  1. Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, ul. Święcickiego 4, 60-781, Poznań, Poland

    Aleksandra Majchrzak-Celińska, Jarosław Paluszczak, Robert Kleszcz, Adam Sherba & Wanda Baer-Dubowska

  2. Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznań, Poland

    Marlena Szalata

  3. Department and Clinic of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Poznań, Poland

    Anna-Maria Barciszewska & Stanisław Nowak

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  1. Aleksandra Majchrzak-Celińska
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  2. Jarosław Paluszczak
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Correspondence to Wanda Baer-Dubowska.

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Majchrzak-Celińska, A., Paluszczak, J., Szalata, M. et al. The methylation of a panel of genes differentiates low-grade from high-grade gliomas. Tumor Biol. 36, 3831–3841 (2015). https://doi.org/10.1007/s13277-014-3025-3

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  • DOI: https://doi.org/10.1007/s13277-014-3025-3

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