DNA repair gene O6-methylguanine-DNA methyltransferase: Promoter hypermethylation associated with decreased expression and G:C to A:T mutations ofp53 in brain tumors

2002 ◽  
Vol 36 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Dong Yin ◽  
Dong Xie ◽  
Wolf-Karsten Hofmann ◽  
Wenxuan Zhang ◽  
Kamlesh Asotra ◽  
...  
Keyword(s):  
Dna Repair ◽  
Brain Tumors ◽  
Dna Methyltransferase ◽  
Promoter Hypermethylation ◽  
Repair Gene ◽  
Methylguanine Dna Methyltransferase ◽  
Dna Repair Gene

Methylenetetrahydrofolate Reductase Genotype in Diffuse Large B-Cell Lymphomas with and without Hypermethylation of the DNA Repair Gene O6-Methylguanine DNA Methyltransferase

2003 ◽  
Vol 18 (3) ◽  
pp. 218-221 ◽  
Author(s):  
G. Toffoli ◽  
D. Rossi ◽  
G. Gaidano ◽  
E. Cecchin ◽  
M. Boiocchi ◽  
...  
Keyword(s):  
Dna Repair ◽  
B Cell ◽  
Dna Methyltransferase ◽  
Methylenetetrahydrofolate Reductase ◽  
B Cell Lymphomas ◽  
Repair Gene ◽  
Mthfr Polymorphisms ◽  
Methylguanine Dna Methyltransferase ◽  
Dna Repair Gene ◽  
Large B Cell

C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been suggested to affect susceptibility to malignant lymphoma, possibly by altering DNA methylation. The DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in diffuse large B-cell lymphomas (DLBCL). We analyzed the MTHFR677 and MTHFR1298 genotypes in 111 DLBCL patients and 465 controls. No significant difference in the frequency of MTHFR polymorphisms between patients and controls and no significant association between MTHFR677 or MTHFR1298 genotypes and methylation of MGMT promoter were observed. These results indicate that MTHFR variants are not related to DLBCL development and MGMT hypermethylation.

Induction of the DNA repair gene O6-methylguanine—DNA methyltransferase by dexamethasone in glioblastomas

2004 ◽  
Vol 101 (4) ◽  
pp. 659-663 ◽  
Author(s):  
Shigeo Ueda ◽  
Toshihiro Mineta ◽  
Yukiko Nakahara ◽  
Hiroaki Okamoto ◽  
Tetsuya Shiraishi ◽  
...  
Keyword(s):  
Dna Repair ◽  
Messenger Rna ◽  
Dna Methyltransferase ◽  
Alkylating Agents ◽  
Malignant Gliomas ◽  
Repair Gene ◽  
Content Type ◽  
Methylguanine Dna Methyltransferase ◽  
Dna Repair Gene ◽  
Fine Print

Object. The DNA repair enzyme O6-methylguanine—DNA methyltransferase (MGMT) inhibits the cytotoxic effect of alkylating agents on tumor cells. The presence of two nonconsensus glucocorticoid-responsive elements in the human MGMT promoter region indicates the potential regulation of MGMT expression by glucocorticoid agents. This study was performed to elucidate whether dexamethasone affects the expression of MGMT in glioblastoma multiforme (GBM) cells, thereby limiting the benefit of chemotherapeutic alkylating agents. Methods. Four GBM cell lines (A172, T98G, U138MG, and U87MG) were exposed to the alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) with or without dexamethasone. The expression levels of MGMT were correlated with the cytotoxic effects of ACNU in GBM cells. In the presence of ACNU alone, dexamethasone alone, and the combination of both agents, messenger RNA expression of MGMT was induced to varying degrees with the highest increases seen in the later conditions. This dexamethasone-dependent induction of the MGMT gene was even observed in U87MG cells in which the promoter is methylated, although the absolute expression of MGMT mRNA was the lowest in that cell line. The induction of MGMT by dexamethasone was associated with an increased resistance of these cells to ACNU. Conclusions. These results indicate that dexamethasone-mediated upregulation of MGMT limits the efficiency of alkylating agents in the treatment of malignant gliomas.

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