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Human brain tumor O 6 ‐methylguanine‐DNA methyltransferase mRNA and its significance as an indicator of selective chloroethylnitrosourea chemotherapy
Author(s) -
Mineura Katsuyoshi,
Yanagisawa Toshiharu,
Watanabe Katsuo,
Kowada Masayoshi,
Yasui Nobuyuki
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961021)69:5<420::aid-ijc12>3.0.co;2-6
Subject(s) - chemotherapy , methyltransferase , messenger rna , glioma , tumor progression , medicine , cancer research , biology , dna , cancer , biochemistry , gene , methylation
O 6 ‐methylguanine‐DNA methyltransferase (MGMT) removes and repairs chloroethylnitrosourea (CENU)‐induced O 6 ‐methylguanine‐DNA by accepting the alkyl group at a cysteine moiety. MGMT activity is, therefore, predictive of resistance or sensitivity to CENU chemotherapy. We measured the levels of MGMT mRNA expression in human brain tumors using a reverse transcription‐polymerase chain reaction (RT‐PCR) method, and studied the significance of MGMT mRNA levels in CENU chemotherapy. The level of MGMT mRNA was represented as a percentage relative to the MGMT mRNA in UI38MG brain tumor cells. Forty‐three patients with brain tumors were entered into the study. High‐grade gliomas had significantly lower levels of MGMT mRNA than did low‐grade gliomas and non‐glial tumors ( p < 0.05 determined by analysis of co‐variance). Out of 14 high‐grade gliomas, 4 had a level of MGMT mRNA below 10%, indicating chemosensitivity to CENU. Out of 11 patients who received CENU chemotherapy, 3 had a partial response. All 3 responders had a low level of MGMT mRNA. The time to tumor progression (TTP) for 6 patients with a level lower than the median was short, but significantly longer than the TTP for 5 patients with a higher level ( p < 0.05 determined by Gehan's Wilcoxon test). These results indicate that a fraction of brain tumors have a low expression of MGMT mRNA, and that the level of MGMT mRNA is a useful indicator of effectiveness in selective CENU chemotherapy. © 1996 Wiley‐Liss, Inc.