O6-methylguanine-DNA methyltransferase protein levels in pediatric brain tumors

Suradej Hongeng; Thomas P. Brent; Robert A. Sanford; Hao Li; Larry E. Kun; Richard L. Heideman

O⁶-methylguanine-DNA methyltransferase protein levels in pediatric brain tumors

Suradej Hongeng, Thomas P. Brent, Robert A. Sanford, Hao Li, Larry E. Kun, Richard L. Heideman

Research output: Contribution to journal › Article › peer-review

Abstract

Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation occurring at the O⁶-position of guanine in DNA. The DNA repair protein O⁶- methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor resistance to CENUs. The current study is the largest report of MGMT levels among newly diagnosed pediatric CNS tumors and the only study that has quantitated MGMT by both biochemical and Western immunoblot assays. Our results show a good correlation between the two methods (r = 0.66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma had the highest level of MGMT, followed by high-grade glioma and low-grade glioma. These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.

Original language	English (US)
Pages (from-to)	2459-2463
Number of pages	5
Journal	Clinical Cancer Research
Volume	3
Issue number	12 I
State	Published - Dec 1997

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "O6-methylguanine-DNA methyltransferase protein levels in pediatric brain tumors",

abstract = "Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation occurring at the O6-position of guanine in DNA. The DNA repair protein O6- methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor resistance to CENUs. The current study is the largest report of MGMT levels among newly diagnosed pediatric CNS tumors and the only study that has quantitated MGMT by both biochemical and Western immunoblot assays. Our results show a good correlation between the two methods (r = 0.66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma had the highest level of MGMT, followed by high-grade glioma and low-grade glioma. These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.",

author = "Suradej Hongeng and Brent, {Thomas P.} and Sanford, {Robert A.} and Hao Li and Kun, {Larry E.} and Heideman, {Richard L.}",

year = "1997",

month = dec,

language = "English (US)",

volume = "3",

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journal = "Clinical Cancer Research",

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publisher = "American Association for Cancer Research Inc.",

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TY - JOUR

T1 - O6-methylguanine-DNA methyltransferase protein levels in pediatric brain tumors

AU - Hongeng, Suradej

AU - Brent, Thomas P.

AU - Sanford, Robert A.

AU - Li, Hao

AU - Kun, Larry E.

AU - Heideman, Richard L.

PY - 1997/12

Y1 - 1997/12

N2 - Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation occurring at the O6-position of guanine in DNA. The DNA repair protein O6- methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor resistance to CENUs. The current study is the largest report of MGMT levels among newly diagnosed pediatric CNS tumors and the only study that has quantitated MGMT by both biochemical and Western immunoblot assays. Our results show a good correlation between the two methods (r = 0.66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma had the highest level of MGMT, followed by high-grade glioma and low-grade glioma. These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.

AB - Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation occurring at the O6-position of guanine in DNA. The DNA repair protein O6- methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor resistance to CENUs. The current study is the largest report of MGMT levels among newly diagnosed pediatric CNS tumors and the only study that has quantitated MGMT by both biochemical and Western immunoblot assays. Our results show a good correlation between the two methods (r = 0.66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma had the highest level of MGMT, followed by high-grade glioma and low-grade glioma. These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.

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SN - 1078-0432

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JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 12 I

ER -

O⁶-methylguanine-DNA methyltransferase protein levels in pediatric brain tumors

Abstract

ASJC Scopus subject areas

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