O(6)-methylguanine-DNA methyltransferase gene (MGMT) expression in human glioblastomas in relation to patient characteristics and p53 accumulation

Int J Cancer. 1999 Aug 20;84(4):416-20. doi: 10.1002/(sici)1097-0215(19990820)84:4<416::aid-ijc15>3.0.co;2-a.

Abstract

Repair of cytotoxic DNA damage by O(6)-methylguanine-DNA methyltransferase (MGMT) is a potentially important factor of chemoresistance to chloroethylnitrosoureas (CENUs), commonly used in the treatment of glioblastoma multiforme (GBM). The value of p53 as a prognostic factor in GBMs remains unclear, but a possible relationship between MGMT gene expression and p53 has been suggested. To further examine these GBM characteristics in vivo, we assessed MGMT gene expression using semi-quantitative RT-PCR and p53 alteration by immuno-histochemistry on a series of 39 GBMs. MGMT gene expression was inversely correlated with age (p < 0.03), consistent with the results of others. Interestingly, tumors from male patients had higher MGMT mRNA amounts than tumors from female patients (p < 0.03). No prognostic implication was observed either for MGMT gene expression or for p53 accumulation. However, MGMT gene expression was significantly lower in p53-altered GBM, regardless of the percentage of positive cells (p < 0.01). Our observation suggests that in human glial tumors, a low level of MGMT gene expression might promote p53 alteration, probably via mutation of its gene. Int. J. Cancer (Pred. Oncol.) 84:416-420, 1999.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Carmustine / therapeutic use
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, p53*
  • Glioma / enzymology*
  • Glioma / genetics*
  • Glioma / mortality
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Male
  • Middle Aged
  • O(6)-Methylguanine-DNA Methyltransferase / analysis
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Predictive Value of Tests
  • Prognosis
  • RNA, Messenger / genetics
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors
  • Survival Analysis
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • O(6)-Methylguanine-DNA Methyltransferase
  • Carmustine