Association between MGMT promoter hypermethylation and p53 mutation in glioblastoma

Cancer Invest. 2009 Oct;27(8):825-9. doi: 10.1080/07357900902783211.

Abstract

O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that removes alkyl groups from the O(6) position of guanine. MGMT is transcriptionally silenced by promoter hypermethylation in several human neoplasia. We used methylation-specific PCR (MSP) to analyze the MGMT promoter methylation status of 50 glioblastoma tumors. Hypermethylation was detected in 24 of 50 (48%) samples. We also analyzed mutant p53 expression by immunohistochemical analysis of glioblastoma tissue samples. A significant association was found between MGMT methylation and p53 mutation status (p< .05). These results suggested that epigenetic inactivation of MGMT plays an important role in the survival of glioblastoma patients and this inactivated gene involved in p53 mutation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / chemistry
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Child
  • CpG Islands*
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / chemistry
  • Glioblastoma / enzymology
  • Glioblastoma / genetics*
  • Humans
  • Immunohistochemistry
  • Iran
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes