DNA repair gene O6-methylguanine-DNA methyltransferase: promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors.

The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) removes alkylating adducts from the O(6) position of guanine and protects cells from cytotoxic and mutagenic effects. Expression of MGMT is decreased in some cancers, which may be the result of methylation of CpG islands of both the promoter and coding regions of the gene. We studied the methylation status of the MGMT promoter in a very large collection of brain tumors (85) using methylation-specific polymerase chain reaction (PCR). Aberrant methylation occurred in 48% of 85 human brain tumor samples. Quantitative real-time PCR showed that expression of MGMT mRNA levels was significantly decreased (P < 0.001) in those brain tumors that had methylation of the promoter region of their MGMT gene. MGMT can prevent G to A mutations by removing alkyl groups from the O(6) position of guanine. We found a significantly increased frequency of G:C to A:T mutations of the p53 gene in brain tumors having a methylated MGMT promoter compared with those having an unmethylated MGMT promoter (P < 0.05), and all the non-CpG dinucleotide G:C to A:T mutations of p53 were in samples with a methylated MGMT promoter.

Yin D ，Xie D ，Hofmann WK ，Zhang W ，Asotra K ，Wong R ，Black KL ，Koeffler HP ... -  《MOLECULAR CARCINOGENESIS》

Hypermethylation of the DNA repair gene MGMT: association with TP53 G:C to A:T transitions in a series of 469 nervous system tumors.

Bello MJ ，Alonso ME ，Amiñoso C ，Anselmo NP ，Arjona D ，Gonzalez-Gomez P ，Lopez-Marin I ，de Campos JM ，Gutierrez M ，Isla A ，Kusak ME ，Lassaletta L ，Sarasa JL ，Vaquero J ，Casartelli C ，Rey JA ... -  《-》

Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis.

Esteller M ，Risques RA ，Toyota M ，Capella G ，Moreno V ，Peinado MA ，Baylin SB ，Herman JG ... -  《CANCER RESEARCH》

Inactivation of DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relation to p53 mutations in esophageal squamous cell carcinoma.

Zhang L ，Lu W ，Miao X ，Xing D ，Tan W ，Lin D ... -  《CARCINOGENESIS》

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis.

Esteller M ，Toyota M ，Sanchez-Cespedes M ，Capella G ，Peinado MA ，Watkins DN ，Issa JP ，Sidransky D ，Baylin SB ，Herman JG ... -  《CANCER RESEARCH》