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

Abstract

O⁶‐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 β2‐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 ≧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.