O⁶-Methylguanine-DNA methyltransferase
(MGMT, alkyltransferase, AGT)

Some papers on MGMT (further additions will be welcomed)

Anda T, Shabani HK, Tsunoda K, Tokunaga Y, Kaminogo M, Shibata S, et al. (2003). Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase pi in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis. Neurol Res, 25, 241-8.

Becker K, Dosch J, Gregel CM, Martin BA and Kaina B. (1996). Targeted expression of human O(6)-methylguanine-DNA methyltransferase (MGMT) in transgenic mice protects against tumor initiation in two-stage skin carcinogenesis. Cancer Res, 56, 3244-9.

Becker K, Gregel C, Fricke C, Komitowski D, Dosch J and Kaina B. (2003). DNA repair protein MGMT protects against N-methyl-N-nitrosourea-induced conversion of benign into malignant tumors. Carcinogenesis, 24, 541-6.

Beranek DT. (1990). Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat Res, 231, 11-30.

Bobola MS, Berger MS, Ellenbogen RG, Roberts TS, Geyer JR and Silber JR. (2001). O6-methylguanine-DNA methyltransferase in pedriatric primary brain tumors: relation to patient and tumor characteristics. Clin. Cancer Res., 7, 613-619.

Chen JM, Zhang YP, Wang C, Sun Y, Fujimoto J and Ikenaga M. (1992). O6-methylguanine-DNA methyltransferase activity in human tumors. Carcinogenesis, 13, 1503-7.

Chen ZP, Yarosh D, Garcia Y, Tampieri D, Mohr G, Malapetsa A, et al. (1999). Relationship between O6-methylguanine-DNA methyltransferase levels and clinical response induced by chloroethylnitrosourea therapy in glioma patients. Can J Neurol Sci, 26, 104-9.

Debiak M, Nikolova T and Kaina B. (2004). Loss of ATM sensitizes against O6-methylguanine triggered apoptosis, SCEs and chromosomal aberrations. DNA Repair (Amst), 3, 359-68.

Dolan ME, Moschel RC and Pegg AE. (1990). 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. Proc Natl Acad Sci U S A, 87, 5368-72.

Dumenco LL, Allay E, Norton K and Gerson SL. (1993). The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase. Science, 259, 219-22.

Dunkern T, Roos W and Kaina B. (2003). Apoptosis induced by MNNG in human TK6 lymphoblastoid cells is p53 and Fas/CD95/Apo-1 related. Mutat Res, 544, 167-72.

Esteller M, Corn PG, Baylin SB and Herman JG. (2001). A gene hypermethylation profile of human cancer. Cancer Res, 61, 3225-9.

Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. (2000). Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med, 343, 1350-4.

Esteller M, Hamilton SR, Burger PC, Baylin SB and Herman JG. (1999). Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res, 59, 793-7.

Gerson SL. (2004). MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer, 4, 296-307.

Hammond LA, Eckardt JR, Kuhn JG, Gerson SL, Johnson T, Smith L, et al. (2004). A randomized phase I and pharmacological trial of sequences of 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide in patients with advanced solid neoplasms. Clin Cancer Res, 10, 1645-56.

Hampson R, Humbert P, Macpherson P, Aquilina G and Karran P. (1997). Mismatch repair defects and O6-methylguanine-DNA methyltransferase expression in acquired resistance to methylating agents in human cells. J. Biol. Chem., 272, 28596-28606.

Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, et al. (2004). Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res, 10, 1871-4.

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. (2005). MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med, 352, 997-1003.

Hermisson M, Klumpp A, Wick W, Wischhusen J, Nagel G, Roos W, et al. (2006). O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells. J Neurochem, 96, 766-76.

Hickman MJ and Samson LD. (1999). Role of mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Proc. Natl. Acad. Sci. USA, 96, 10764-10769.

Hickman MJ and Samson LD. (2004). Apoptotic signaling in response to a single type of DNA lesion, O(6)-methylguanine. Mol Cell, 14, 105-16.

Kaina B, Fritz G, Mitra S and Coquerelle T. (1991). Transfection and expression of human O6-methylguanine-DNA methyltransferase (MGMT) cDNA in Chinese hamster cells: the role of MGMT in protection against the genotoxic effects of alkylating agents. Carcinogenesis, 12, 1857-67.

Kaina B, Ziouta A, Ochs K and Coquerelle T. (1997). Chromosomal instability, reproductive cell death and apoptosis induced by O6-methylguanine in Mex-, Mex+ and methylation-tolerant mismatch repair compromised cells: facts and models. Mutat Res, 381, 227-41.

Karran P and Bignami M. (1994). DNA damage tolerance, mismatch repair and genome instability. Bioessays, 16, 833-9.

Kat A, Thilly WG, Fang WH, Longley MJ, Li GM and Modrich P. (1993). An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc Natl Acad Sci U S A, 90, 6424-8.

Margison GP and Santibanez-Koref MF. (2002). O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy. Bioessays, 24, 255-66.

Meikrantz W, Bergom MA, Memisoglu A and Samson L. (1998). O6-alkylguanine DNA lesions trigger apoptosis. Carcinogenesis, 19, 369-72.

Ochs K and Kaina B. (2000). Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res, 60, 5815-24.

Paz MF, Yaya-Tur R, Rojas-Marcos I, Reynes G, Pollan M, Aguirre-Cruz L, et al. (2004). CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res, 10, 4933-8.

Pegg AE. (2000). Repair of O(6)-alkylguanine by alkyltransferases. Mutat Res, 462, 83-100.

Pegg AE, Boosalis M, Samson L, Moschel RC, Byers TL, Swenn K, et al. (1993). Mechanism of inactivation of human O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine. Biochemistry, 32, 11998-2006.

Pepponi R, Marra G, Fuggetta MP, Falcinelli S, Pagani E, Bonmassar E, et al. (2003). The effect of O6-alkylguanine-DNA alkyltransferase and mismatch repair activities on the sensitivity of human melanoma cells to temozolomide, 1,3-bis(2-chloroethyl)1-nitrosourea, and cisplatin. J Pharmacol Exp Ther, 304, 661-8.

Preuss I, Eberhagen I, Haas S, Eibl RH, Kaufmann M, von Minckwitz G, et al. (1995). O6-methylguanine-DNA methyltransferase activity in breast and brain tumors. Int J Cancer, 61, 321-6.

Preuss I, Thust R and Kaina B. (1996). Protective effect of O6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxic and recombinogenic activity of different antineoplastic drugs. Int J Cancer, 65, 506-12.

Roos W, Baumgartner M and Kaina B. (2004). Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas/CD95/Apo-1. Oncogene, 23, 359-67.

Scudiero DA, Meyer SA, Clatterbuck BE, Mattern MR, Ziolkowski CH and Day RS, 3rd. (1984). Sensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas. Cancer Res, 44, 2467-74.

Silber JR, Blank A, Bobola MS, Ghatan S, Kolstoe DD and Berger MS. (1999). O6-methylguanine-DNA methyltransferase-deficient phenotype in human gliomas: frequency and time to tumor progression after alkylating agent-based chemotherapy. Clin Cancer Res, 5, 807-14.

Sklar RM and Strauss B. (1981). Removal of O6-methylguanine from DNA of normal and xeroderma pigmentosum-derived lymphoblastoid lines. Nature, 289, 417-420.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med, 352, 987-96.

Tominaga Y, Tsuzuki T, Shiraishi A, Kawate H and Sekiguchi M. (1997). Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA-repair, methyltransferase, had been disrupted by gene targeting. Carcinogenesis, 18, 889-96.

Tsaryk R, Fabian K, Thacker J and Kaina B. (2005). Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide. Cancer Lett.

Wischhusen J, Naumann U, Ohgaki H, Rastinejad F and Weller M. (2003). CP-31398, a novel p53-stabilizing agent, induces p53-dependent and p53-independent glioma cell death. Oncogene, 22, 8233-45.