Detection of MGMT promoter methylation in normal individuals is strongly associated with the T allele of the rs16906252 MGMT promoter single nucleotide polymorphism

Methylation of the CpG island in the MGMT promoter region is a frequent event in several cancer types including colorectal cancer, lung cancer, lymphoma, and glioblastoma. A correlation between methylation and the T allele of the rs16906252 single nucleotide polymorphism (SNP) in colorectal carcinom...

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Bibliographic Details
Published in:Cancer prevention research (Philadelphia, Pa.) Pa.), 2009-10, Vol.2 (10), p.862-867
Main Authors: Candiloro, Ida L M, Dobrovic, Alexander
Format: Article
Language:English
Subjects:
Alleles
Base Sequence
DNA Methylation - genetics
DNA Modification Methylases - genetics
DNA Repair Enzymes - genetics
Genetic Predisposition to Disease
Genotype
Humans
Neoplasms - genetics
Polymorphism, Single Nucleotide
Promoter Regions, Genetic - genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Proteins - genetics
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Summary:Methylation of the CpG island in the MGMT promoter region is a frequent event in several cancer types including colorectal cancer, lung cancer, lymphoma, and glioblastoma. A correlation between methylation and the T allele of the rs16906252 single nucleotide polymorphism (SNP) in colorectal carcinomas has previously been reported. As aberrant MGMT methylation can be an early event in tumor development, we tested the hypothesis that normal individuals possessing the T allele may be predisposed to somatic methylation at the MGMT promoter. Peripheral blood monononuclear cell DNA from 89 normal, healthy individuals was genotyped at rs1690625 and assessed for the methylation status of the MGMT promoter region using independent quantitative methodologies capable of detecting low-level methylation: MethyLight and Sensitive Melting Analysis after Real-time Methylation-Specific PCR (SMART-MSP). There was a strong association between presence of the T allele and detectable methylation (P = 0.00005) in the peripheral blood DNA. Furthermore, when a MSP assay flanking the SNP was used to amplify methylated sequences in heterozygotes, only the T allele was methylated. Thus, detectable somatic methylation of the MGMT promoter in normal individuals is strongly associated with the T allele of the rs16906252 MGMT promoter SNP.
ISSN:1940-6207
1940-6215
DOI:10.1158/1940-6207.CAPR-09-0056