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DNA repair gene O 6 ‐methylguanine‐DNA methyltransferase: Promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors
Author(s) -
Yin Dong,
Xie Dong,
Hofmann WolfKarsten,
Zhang Wenxuan,
Asotra Kamlesh,
Wong Rex,
Black Keith L,
Koeffler H. Phillip
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10094
Subject(s) - biology , cpg site , methylation , microbiology and biotechnology , methyltransferase , o 6 methylguanine dna methyltransferase , dna methylation , dna methyltransferase , promoter , guanine , gene , dna repair , dna , cancer research , gene expression , genetics , nucleotide
Abstract 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. © 2002 Wiley‐Liss, Inc.