title: The methylation of a panel of genes differentiates low-grade from high-grade gliomas.
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.
authors.affiliation: Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, ul. Święcickiego 4, 60-781, Poznań, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Majchrzak-Celińska
authors.forename: Jarosław
authors.initials: J
authors.lastname: Paluszczak
authors.forename: Marlena
authors.initials: M
authors.lastname: Szalata
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Barciszewska
authors.forename: Stanisław
authors.initials: S
authors.lastname: Nowak
authors.forename: Robert
authors.initials: R
authors.lastname: Kleszcz
authors.forename: Adam
authors.initials: A
authors.lastname: Sherba
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D050993:GATA6 Transcription Factor / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; C493729:Runx3 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes