Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma

Promoter hypermethylation of the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to compare three distinct yet related indices for...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2006-10, Vol.5 (10), p.2531-2539
Main Authors: Maxwell, Jill A, Johnson, Stewart P, Quinn, Jennifer A, McLendon, Roger E, Ali-Osman, Francis, Friedman, Allan H, Herndon, 2nd, James E, Bierau, Katja, Bigley, Joseph, Bigner, Darell D, Friedman, Henry S
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
AGT
Brain Neoplasms - enzymology
DNA Methylation
Female
glioma
Glioma - enzymology
Humans
Immunohistochemistry
Male
Middle Aged
MSP
O-Methylguanine-DNA Methyltransferase - biosynthesis
O-Methylguanine-DNA Methyltransferase - genetics
O-Methylguanine-DNA Methyltransferase - metabolism
Polymerase Chain Reaction
Promoter Regions, Genetic
resistance
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Summary:Promoter hypermethylation of the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to compare three distinct yet related indices for measuring AGT to determine if these assays could be used interchangeably when AGT status is to be used to guide chemotherapeutic decisions. Real-time methylation-specific PCR (MSP), assessed as the ratio of methylated AGT copies to internal β-actin control, was used to quantitate AGT hypermethylation in 32 glioma samples. Data were compared with AGT enzyme activity as well as immunohistochemical detection of AGT protein from the same samples. Hypermethylation of the AGT promoter was detected in 19 of 31 (61%) samples evaluable by MSP. Low-level AGT, defined as
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-06-0106