O-6-methylguanine-DNA methyltranspherase gene expression in gliomas by means of real-time quantitative RT-PCR and clinical response to nitrosoureas

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 1. 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 : I 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. (C) 2002 Wiley-Liss, Inc.