title: DNA methylation analysis of benign and atypical meningiomas: correlation between RUNX3 methylation and WHO grade.
abstract: OBJECTIVE
  Although meningiomas are common central nervous system tumors, the biomarkers allowing early diagnosis and progression are still needed. The aim of this study was to evaluate the methylation status of 12 cancer-related genes, namely ERCC1, hMLH1, ATM, CDKN2B (p15INK4B), p14ARF, CDKN2A (p16INK4A), RASSF1A, RUNX3, GATA6, NDRG2, PTEN, and RARβ, in 44 meningioma samples of WHO grade I and II.
  
  
  METHODS
  All genes were analyzed using methylation-specific polymerase chain reaction, while pyrosequencing (PSQ) was used to study NDRG2 promoter methylation.
  
  
  RESULTS
  The most frequently methylated genes in both types of meningiomas were p14ARF, RASSF1A, and p15INK4B. RUNX3, GATA6, and p16INK4A were methylated to a lesser extent, whereas ATM and RARβ were found to be methylated in a marginal number of patients. The ERCC1, hMLH1, NDRG2, and PTEN genes were unmethylated in all cases. Although tumors of the same grade according to WHO criteria had different genes methylated, the number of methylated genes for each individual patient was low. RUNX3 methylation significantly correlated with meningioma WHO grade, therefore, can be considered as a potential indicator of tumor aggressiveness. The sequence of NDRG2 chosen for PSQ analysis was found methylated in the majority of meningiomas; however, the methylation level was only slightly elevated as compared to non-cancerous brain.
  
  
  CONCLUSIONS
  Overall, the results of this study confirm that DNA methylation plays an important role in the pathogenesis of meningiomas. Further investigations, particularly concerning RUNX3 methylation, are necessary in order to assess the clinical usefulness of the methylation analysis of the studied genes.
authors: Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.
authors: Aleksandra
authors: A
authors: Majchrzak-Celińska
authors: Jarosław
authors: J
authors: Paluszczak
authors: Marlena
authors: M
authors: Szalata
authors: Anna-Maria
authors: AM
authors: Barciszewska
authors: Stanisław
authors: S
authors: Nowak
authors: Wanda
authors: W
authors: Baer-Dubowska
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C466228:NDRG2 protein, human; C493729:Runx3 protein, human; D025521:Tumor Suppressor Proteins
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