O6-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 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.
Tanaka
Satoshi
S
Department of Neurosurgery, The Kitasato Institute Medical Center Hospital, Kitamoto, Japan. tanaka-s@kitasato.or.jp
Kobayashi
Ikuo
I
Utsuki
Satoshi
S
Oka
Hidehiro
H
Fujii
Kiyotaka
K
Watanabe
Takashi
T
Nagashima
Tadashi
T
Hori
Tomokatsu
T
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D015376:Nimustine / Q000627:therapeutic use*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014158:Transcription, Genetic; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001613:beta 2-Microglobulin; D015376:Nimustine; D019853:O(6)-Methylguanine-DNA Methyltransferase