MGMT: its role in cancer aetiology and cancer therapeutics

Inactivation of the DNA-Repair GeneMGMTand the Clinical Response of Gliomas to Alkylating Agents

2000 • 2,127 citations

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

2003 • 1,261 citations

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia.

1999 • 1,252 citations

Repair of O6-alkylguanine by alkyltransferases

2000 • 569 citations

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis.

2000 • 529 citations

Structure, Function, and Inhibition of O6-Alkylguanine-DNA Alkyltransferase

1995 • 502 citations

Persistence of O 6-Ethylguanine in Rat-Brain DNA: Correlation with Nervous System-Specific Carcinogenesis by Ethylnitrosourea

1974 • 495 citations

Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents.

1990 • 460 citations

Epstein-Barr Virus-Positive Gastric Carcinoma Demonstrates Frequent Aberrant Methylation of Multiple Genes and Constitutes CpG Island Methylator Phenotype-Positive Gastric Carcinoma

2002 • 327 citations

DNA damage tolerance, mismatch repair and genome instability

1994 • 308 citations

Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study.

1998 • 300 citations

Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine.

1990 • 292 citations

Hypermethylation of the DNA Repair Gene O6-Methylguanine DNA Methyltransferase and Survival of Patients With Diffuse Large B-Cell Lymphoma

2002 • 289 citations

Phase I Trial of Temozolomide Plus O⁶-Benzylguanine for Patients With Recurrent or Progressive Malignant Glioma

2005 • 288 citations

Comparison of O⁶-alkylguanine-DNA alkyltransferase activity based on cellular DNA content in human, rat and mouse tissues

1986 • 277 citations

Mammalian base excision repair and DNA polymerase beta

1998 • 275 citations

The Prevention of Thymic Lymphomas in Transgenic Mice by Human O ⁶ -Alkylguanine-DNA Alkyltransferase

1993 • 238 citations

Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to 1,3-bis(2-chloroethyl)nitrosourea.

1996 • 236 citations

Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C -> A:T mutations of the TP53 tumor suppressor gene

2001 • 231 citations

Evidence that the number of hematopoietic stem cells per animal is conserved in mammals

2002 • 229 citations

Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding

2000 • 219 citations

Phase I trial of O6-benzylguanine for patients undergoing surgery for malignant glioma.

1998 • 214 citations

Methylation of Discrete Regions of the O⁶-Methylguanine DNA Methyltransferase (MGMT) CpG Island Is Associated with Heterochromatinization of the MGMT Transcription Start Site and Silencing of the Gene

1997 • 214 citations

Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli.

1994 • 198 citations

Chromosomal instability, reproductive cell death and apoptosis induced by O6-methylguanine in Mex−, Mex+ and methylation-tolerant mismatch repair compromised cells: facts and models

1997 • 190 citations

Alkylation of deoxyribonucleic acid in vivo in various organs of C57BL mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma. Some applications of high-pressure liquid chromatography

1978 • 177 citations

Safety and Efficacy of Temozolomide in Patients With Recurrent Anaplastic Oligodendrogliomas After Standard Radiotherapy and Chemotherapy

2001 • 176 citations

Human tumor cell strains defective in the repair of alkylation damage

1980 • 169 citations

DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents

1999 • 146 citations

O6-methylguanine-DNA methyltransferase protects against nitrosamine-induced hepatocarcinogenesis.

1993 • 143 citations

O6-Alkylguanine-DNA alkyltransferase activity correlates with the therapeutic response of human rhabdomyosarcoma xenografts to 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea.

1985 • 137 citations

Efficient repair of O6-ethylguanine, but not O4-ethylthymine or O2-ethylthymine, is dependent upon O6-alkylguanine-DNA alkyltransferase and nucleotide excision repair activities in human cells.

1992 • 135 citations

Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes

1998 • 132 citations

Crystal structure of the human O6-alkylguanine-DNA alkyltransferase

2000 • 131 citations

Transgenic expression of human MGMT protects against azoxymethane-induced aberrant crypt foci and G to A mutations in the K-ras oncogene of mouse colon

1995 • 130 citations

Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice.

1997 • 130 citations

O6-benzylguanine: a clinical trial establishing the biochemical modulatory dose in tumor tissue for alkyltransferase-directed DNA repair.

1999 • 127 citations

Direct reversal of DNA damage by mutant methyltransferase protein protects mice against dose-intensified chemotherapy and leads to in vivo selection of hematopoietic stem cells.

2000 • 124 citations

Cloning of theE. coliO⁶-methylguanine and methylphosphotriester methyltransferase gene using a functional DNA repair assay

1985 • 124 citations

O6-Alkylguanine-DNA alkyltransferase and sensitivity to procarbazine in human brain-tumor xenografts

1989 • 122 citations

Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base excision repair genes

1996 • 121 citations

Limiting numbers of G156A O6-methylguanine–DNA methyltransferase-transduced marrow progenitors repopulate nonmyeloablated mice after drug selection

2000 • 121 citations

ENU Mutagenesis: Analyzing Gene Function in Mice

2001 • 120 citations

O6-methylguanine-DNA methyltransferase in human normal and tumor tissue from brain, lung, and ovary.

1991 • 115 citations

Phase I Trial of Carmustine Plus O6-Benzylguanine for Patients With Recurrent or Progressive Malignant Glioma

2000 • 112 citations

Methylation ofO6-methylguanine-DNA methyltransferase gene is associated significantly withK-ras mutation, lymph node invasion, tumor staging, and disease free survival in patients with gastric carcinoma

2001 • 110 citations

Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancer.

2000 • 106 citations

O(6)-Methylguanine-DNA methyltransferase promoter hypermethylation shifts the p53 mutational spectrum in non-small cell lung cancer.

2001 • 104 citations

Isolation of human O6-alkylguanine-DNA alkyltransferase mutants highly resistant to inactivation by O6-benzylguanine.

1998 • 94 citations

Sequential tumor biopsies in early phase clinical trials of anticancer agents for pharmacodynamic evaluation.

2001 • 93 citations

Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase

2000 • 89 citations

Targeted expression of human O(6)-methylguanine-DNA methyltransferase (MGMT) in transgenic mice protects against tumor initiation in two-stage skin carcinogenesis.

1996 • 86 citations

In vivo selection of MGMT(P140K) lentivirus–transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning

2003 • 86 citations

Role of polymorphisms in codons 143 and 160 of the O6-alkylguanine DNA alkyltransferase gene in lung cancer risk.

2000 • 85 citations

Inactivation of the DNA repair gene O⁶‐methylguanine‐DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B₁‐DNA adducts and p53 mutation in hepatocellular carcinoma

2002 • 83 citations

The DNA repair protein, O6-Methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein

2002 • 83 citations

Detection and Measurement of Nucleotide Excision Repair Synthesis by Mammalian Cell Extracts in Vitro

1995 • 82 citations

O6-benzylguanine in humans: metabolic, pharmacokinetic, and pharmacodynamic findings.

1998 • 82 citations

Conserved structural motifs governing the stoichiometric repair of alkylated DNA by O6-alkylguanine-DNA alkyltransferase

2000 • 80 citations

Lack of the DNA repair protein O6-methylguanine-DNA methyltransferase in histologically normal brain adjacent to primary human brain tumors.

1996 • 78 citations

In vivo selection of MGMT(P140K) lentivirus–transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning

2003 • 77 citations

Reduced lung tumorigenesis in human methylguanine DNAmethyltransferase transgenic mice achieved by expression of transgene within the target cell

1999 • 77 citations

High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

1992 • 74 citations

N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea sensitivity in mismatch repair-defective human cells.

1998 • 73 citations

Activation of human O6-methylguanine-DNA methyltransferase gene by glucocorticoid hormone

1999 • 72 citations

Synergistic efficacy of O6benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in a human colon cancer xenograft completely resistant to BCNU alone

1993 • 72 citations

Lentiviral Transduction of P140K MGMT into Human CD34+ Hematopoietic Progenitors at Low Multiplicity of Infection Confers Significant Resistance to BG/BCNU and Allows Selection in Vitro

2002 • 69 citations

Intracellular localization and intercellular heterogeneity of the human DNA repair protein O 6 -methylguanine-DNA methyltransferase

1996 • 68 citations

Specific Recognition of O⁶-Methylguanine in DNA by Active Site Mutants of Human O⁶-Methylguanine-DNA Methyltransferase

1997 • 67 citations

Rapid repair of O6-methylguanine-DNA adducts protects transgenic mice from N-methylnitrosourea-induced thymic lymphomas.

1994 • 66 citations

O 6 -Alkylguanine-DNA Alkyltransferase: A Target for the Modulation of Drug Resistance

1995 • 66 citations

Alkylation of deoxyribonucleic acid in vivo in various organs of c57bl mice by the carcinogens n-methyl-n-nitrosourea, n-ethyl-n- -nitrosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma.

1978 • 65 citations

Delta MGMT-Transduced Bone Marrow Infusion Increases Tolerance to O6-Benzylguanine and 1,3-Bis(2-chloroethyl)1-nitrosourea and Allows Intensive Therapy of 1,3-Bis(2-chloroethyl)-1-nitrosourea-Resistant Human Colon Cancer Xenografts

1999 • 62 citations

Regulation of the HumanO 6-Methylguanine-DNA Methyltransferase Gene by Transcriptional Coactivators cAMP Response Element-binding Protein-binding Protein and p300

2000 • 60 citations

Genetic polymorphism of human O6-alkylguanine-DNA alkyltransferase

1999 • 59 citations

Influence of S -Adenosylmethionine Pool Size on Spontaneous Mutation, Dam Methylation, and Cell Growth of Escherichia coli

1999 • 58 citations

Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum.

2002 • 58 citations

Aberrant Silencing of the CpG Island-Containing Human O⁶-Methylguanine DNA Methyltransferase Gene Is Associated with the Loss of Nucleosome-Like Positioning

1997 • 58 citations

Novel O⁶-methylguanine-DNA methyltransferase SNPs: A frequency comparison of patients with familial melanoma and healthy individuals in Sweden

2002 • 57 citations

Spontaneous hepatocellular carcinoma is reduced in transgenic mice overexpressing human O ⁶ - methylguanine-DNA methyltransferase

2001 • 55 citations

Protein phosphorylation is a regulatory mechanism for O6-alkylguanine-DNA alkyltransferase in human brain tumor cells.

2000 • 52 citations

Deficient expression ofO 6-Methylguanine-DNA methyltransferase combined with mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human biliary tract carcinoma

2002 • 51 citations

Mutations ofO6-methylguanine-DNA methyltransferase gene in esophageal cancer tissues from Northern China

1997 • 49 citations

Interactions between methylating and pyridyloxobutylating agents in A/J mouse lungs: implications for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis.

2001 • 47 citations

DNA methyl-adduct dosimetry and O⁶-alkylguanine-DNA alkyl transferase activity determinations in rat mammary carcinogenesis by procarbazine and N-methylnitrosourea

1990 • 45 citations

Modulation of nitrosourea resistance in human colon cancer by O6-methylguanine

1992 • 45 citations

Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial

1991 • 44 citations

Effect of Sequence Context on O⁶-Methylguanine Repair and Replication in Vivo

2001 • 44 citations

Mice over-expressing human O6alkylguanine-DNA alkyltransferase selectively reduce O6methylguanine mediated carcinogenic mutations to threshold levels after N-methyl-N-nitrosourea

1999 • 44 citations

Cytoplasmic sequestration of an O ⁶ -methylguanine-DNA methyltransferase enhancer binding protein in DNA repair-deficient human cells

1997 • 41 citations

Affinity purification and characterization of humanO⁶-alkylguanine-DNA aikyltransferase complexed with BCNU-treated, synthetic oligonudeotide

1989 • 41 citations

Effect of O⁶‐(4‐bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model

2002 • 40 citations

Contribution of O⁶‐methylguanine‐DNA methyltransferase to monofunctional alkylating‐agent resistance in human brain tumor—derived cell lines

1995 • 39 citations

Temozolomide for recurrent high-grade glioma

2001 • 38 citations

Prolonged inhibition of O(6)-methylguanine DNA methyltransferase in human tumor cells by O(6)-benzylguanine in vitro and in vivo.

1999 • 38 citations

Isolation and characterization of cDNA and genomic sequences for mouse O⁶-methylguanine-DNA methyltransferase

1992 • 36 citations

Myeloablation is not required to select and maintain expression of the drug-resistance gene, mutant MGMT, in primary and secondary recipients

2003 • 36 citations

The nuclear targeting and nuclear retention properties of a human DNA repair protein O6-methylguanine-DNA methyltransferase are both required for its nuclear localization: the possible implications.

1996 • 35 citations

Engineering human DNA alkyltransferases for gene therapy using random sequence mutagenesis.

1998 • 34 citations

Specificity of bischloroethylnitrosourea-induced mutation in a Chinese hamster ovary cell line transformed to express human O6-alkylguanine-DNA alkyltransferase.

1993 • 33 citations

Repair of O6-alkylguanine during DNA synthesis in murine bone marrow hematopoietic precursors.

1987 • 32 citations

Overexpression of human O6-alkylguanine DNA alkyltransferase (AGT) prevents MNU induced lymphomas in heterozygous p53 deficient mice

2001 • 31 citations

Determinants ofO6-alkylguanine-DNA alkyltransferase activity in normal and tumour tissue from human colon and rectum

2000 • 30 citations

Inactivation of O⁶‐Methylguanine‐DNA Methyltransferase in Human Lung Adenocarcinoma Relates to High‐grade Histology and Worse Prognosis among Smokers

2002 • 29 citations

Analysis of N-methyl-N-nitrosourea-induced mutations in a shuttle vector plasmid propagated in mouse O6-methylguanine-DNA methyltransferase-deficient cells in comparison with proficient cells.

1991 • 28 citations

In vivo formation and repair of O⁶ in human leukocyte DNA after intravenous exposure to dacarbazine

1991 • 27 citations

Modulation of O6-alkylguanine alkyltransferase-directed DNA repair in metastatic colon cancers.

1995 • 27 citations

Chemotherapy-induced O(6)-benzylguanine-resistant alkyltransferase mutations in mismatch-deficient colon cancer.

2002 • 26 citations

Novel genetic polymorphisms in DNA repair genes: O6-methylguanine-DNA methyltransferase (MGMT) andN-methylpurine-DNA glycosylase (MPG) in lung cancer patients from Poland

1999 • 26 citations

Role of cytochrome P450 isoenzymes in metabolism of O(6)-benzylguanine: implications for dacarbazine activation.

2001 • 26 citations

Role of codon 160 in the sensitivity of human O6-alkylguanine-DNA alkyltransferase to O6-benzylguanine

1999 • 26 citations

Lack of evidence for a polymorphism at codon 160 of human O6-alkylguanine-DNA alkyltransferase gene in normal tissue and cancer.

1999 • 26 citations

New cytotoxic agents for the treatment of metastatic malignant melanoma: temozolomide and related alkylating agents in combination with guanine analogues to abrogate drug resistance.

2000 • 24 citations

Potentiation of lymphomagenesis by methylnitrosourea in mice transgenic for LMO1 is blocked by O6-alkylguanine DNA-alkyltransferase

1997 • 23 citations

MGMT Expression in Murine Bone Marrow Is a Major Determinant of Animal Survival After Alkylating Agent Exposure

2001 • 21 citations

Transgenic expression of human MGMT blocks the hypersensitivity of PMS2-deficient mice to low dose MNU thymic lymphomagenesis

1999 • 21 citations

Applied molecular evolution of O ⁶ -benzylguanine-resistant DNA alkyltransferases in human hematopoietic cells

2001 • 20 citations

Differential sensitivity of human and mouse alkyltransferase to O6-benzylguanine using a transgenic model.

1996 • 18 citations

Eradication of human medulloblastoma tumor xenografts with a combination of O6-benzyl-2'-deoxyguanosine and 1,3-bis(2-chloroethyl)1-nitrosourea.

1999 • 17 citations

Long-Term Follow-up in Managing Anaplastic Astrocytoma by Multimodality Approach With Surgery Followed by Postoperative Radiotherapy and PCV-Chemotherapy

2002 • 15 citations

Site-directed mutation of the Escherichia coli ada gene: effects of substitution of methyl acceptor cysteine-321 by histidine in Ada protein

1989 • 15 citations

Differential expression of O 6 -methylguanine-DNA methyltransferase during diethylnitrosamine-induced carcinogenesis and liver regeneration in Sprague-Dawley male rats

1999 • 14 citations

Cell type-specific induction of O 6 -alkylguanine-DNA alkyltransferase mRNA expression in rat liver during regeneration, inflammation and preneoplasia

2001 • 12 citations

Adenoviral transfer of antisenses or ribozyme to O6-methylguanine-DNA methyltransferase mRNA in brain-tumor model resistant to chloroethyl-nitrosourea.

2002 • 11 citations

Organization and Expression of the Mouse Gene for DNA Repair Methyltransferase

1996 • 11 citations

Acquired resistance to O 6 -benzylguanine plus chloroethylnitrosoureas in human breast cancer

1999 • 11 citations

Ribozyme and free alkylated base: a dual approach for sensitizing Mex+ cells to the alkylating antineoplastic drug

2000 • 10 citations

Repair of synthetic oligonucleotides containing O6-methylguanine, O6-ethylguanine and O4-methylthymine, by O6-alkylguanine-DNA alkyltransferase.

1987 • 9 citations

O6-alkylguanine-DNA alkyltransferase DNA repair in mycobacteria: pathogenic and non-pathogenic species differ

2002 • 8 citations