O6-methylguanine-DNA methyltranspherase gene expression in gliomas by means of real-time quantitative RT-PCR and clinical response to nitrosoureas

Int J Cancer. 2003 Jan 1;103(1):67-72. doi: 10.1002/ijc.10757.

Abstract

O(6)-methylguanine-DNA methyltransferase (MGMT) mRNA expressions were examined in 100 neuroepithelial tumors by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using SYBR Green I. The mean relative quantitation value of MGMTmRNA normalized to the level of beta2-microglobulin for 100 tumors was 5.3 +/- 11.2. The mean value of 41 glioblastomas was significantly higher than that for the other 59 tumors (p = 0.0008 by Student's t-test). In contrast, the means of 19 low-grade gliomas and 12 medulloblastomas were significantly lower than that of other tumors (p = 0.0282 and p = 0.0456 by Student's t-test). Among the 55 retrospective patients who had been treated with 1-(4-amino-2-methyl-5-pyrimidynyl)methyl-3-(2-chloroethyl)- 3-nitrosourea hydrochloride (ACNU), the value was a significant independent predictor of the effect of initial therapy with ACNU (p = 0.0007 by Mann-Whitney U-test) and the survival period (p = 0.0175 by Wald test). The value >or=1 was the most significant factor in predicting the initial effect of treatment by multi-variant regression analysis (p < 0.0001). These results suggest that our individual adjuvant therapy based on MGMTmRNA expression may be improved by the application of real-time quantitative RT-PCR.

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glioma / drug therapy*
  • Glioma / enzymology
  • Glioma / genetics
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / genetics
  • Nimustine / therapeutic use*
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Transcription, Genetic
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / metabolism

Substances

  • Antineoplastic Agents
  • RNA, Messenger
  • RNA, Neoplasm
  • beta 2-Microglobulin
  • Nimustine
  • O(6)-Methylguanine-DNA Methyltransferase