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

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• 作者：Aleksandra Majchrzak-Celińska ; Jaros?aw Paluszczak ; Marlena Szalata…
• 关键词：Glioma ; DNA methylation biomarkers ; RASSF1A ; RUNX3 ; GATA6 ; MGMT
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：36
• 期：5
• 页码：3831-3841
• 全文大小：1,540 KB
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• 作者单位：Aleksandra Majchrzak-Celińska (1)
  Jaros?aw Paluszczak (1)
  Marlena Szalata (2)
  Anna-Maria Barciszewska (3)
  Stanis?aw Nowak (3)
  Robert Kleszcz (1)
  Adam Sherba (1)
  Wanda Baer-Dubowska (1)
  
  1. Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, ul. ?wi?cickiego 4, 60-781, Poznań, Poland
  2. Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznań, Poland
  3. Department and Clinic of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Poznań, Poland
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

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.