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

Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma. Research Abstract Details 

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Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma. Abstract Text:

Jill A Maxwell,Stewart P Johnson,Jennifer A Quinn,Roger E McLendon,Francis Ali-Osman,Allan H Friedman,James E Herndon,Katja Bierau,Joseph Bigley,Darell D Bigner,Henry S Friedman,

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 beta-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 <20% nuclear AGT staining by immunohistochemistry, was found in 10 of 32 samples (31%), whereas 12 of 32 (38%) had low levels of AGT activity. Correlation of immunohistochemistry to AGT activity was statistically significant (P = 0.014) as was the correlation of immunohistochemistry to MSP (P = 0.043), whereas MSP compared with AGT activity (P = 0.246) was not significant. Cross-tabulation of immunohistochemistry and MSP data based on prognostic groups, where good prognosis was represented by an immunohistochemistry of <20% and an MSP ratio >12, showed no significant relationship (P = 0.214), suggesting that one assay cannot be used interchangeably for another. The observed discordance between respective measures of AGT based on prognosis supports further standardization of AGT assays designed to guide therapeutic practice. The data also suggest that consideration be given to the large population of AGT-expressing cells within samples when therapeutic strategies based on tumor methylation are used.

Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma. Publishing Authors By Initials

JA Maxwell,SP Johnson,JA Quinn,RE McLendon,F Ali-Osman,AH Friedman,JE Herndon,K Bierau,J Bigley,DD Bigner,HS Friedman,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: base sequence: regulatory sequences, nucleic acid: promoter regions (genetics) research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: base sequence: regulatory sequences, nucleic acid: promoter regions (genetics) research

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Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular cancer therapeutics

VOLUME: 5

Page Numbers: 2531-9

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 3

MONTH: Oct

YEAR: 2006

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 101132535

Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma. Keywords Mesh Terms:

KEYWORDS: Promoter Regions (Genetics)

MESH TERMS: metabolism

Chemical & Substance for Abstract: Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma. Information

Substance Name: O(6)-Methylguanine-DNA Methyltransferase

Registry Number: EC 2.1.1.63

Grant and Affiliation Information for Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma.

AFFILIATION: Department of Surgery, Duke University Medical Center, Box 3624, Durham, NC 27710, USA.

Country: United States

AGENCY: United States NINDS

GRANT: 2R01 NS-30245-17A1

ACRONYM: NS

MEDLINETA: Mol Cancer Ther

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