PURPOSE Because O(6)-methylguanine-DNA methyltransferase (MGMT) plays an essential role in repairing DNA damage caused by environmental alkylating chemicals, we were interested in determining whether we could see any obvious changes in the properties of colorectal cancers (CRCs) in which the MGMT gene had been silenced by hypermethylation and hence in which very few MGMT protein molecules were ...

Methylation of the O-methylguanine-DNA methyltransferase (MGMT) gene promoter (i.e., gene silencing) occurs in 40% to 50% of patients with glioblastoma and predicts benefit from temozolomide chemotherapy; when unmethylated, MGMT repairs DNA damage induced by temozolomide, contributing to chemoresistance. In this study, we tested the hypothesis that MGMT is regulated by p53 in astrocytic cells, ...

Alkylation of DNA at the O6-position of guanine is one of the most critical events leading to mutation, cancer, and cell death. The enzyme O6-methylguanine-DNA methyltransferase repairs O6-methylguanine as well as a minor methylated base, O4-methylthymine, in DNA. Mouse lines deficient in the methyltransferase (MGMT) gene are hypersensitive to both the killing and to the tumorigenic effects of ...

A combined therapy of the alkylating agent temozolomide (TMZ) and radiotherapy is standard treatment, and it improves the survival of patients with newly diagnosed glioblastoma (GBM). The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) removes the most cytotoxic lesions generated by TMZ, O(6)-methylguanine, establishing MGMT as one of the most important DNA repair mechanisms o...

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with a poor prognosis. Current standard treatment includes chemotherapy with the DNA-alkylating agent temozolomide concomitant with surgical resection and/or irradiation. However, a number of cases are resistant to temozolomide-induced DNA damage due to elevated expression of the DNA repair enzyme O(6)-methylguanine-DNA me...

Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter (i.e., gene silencing) occurs in 40% to 50% of patients with glioblastoma and predicts benefit from temozolomide chemotherapy; when unmethylated, MGMT repairs DNA damage induced by temozolomide, contributing to chemoresistance. In this study, we tested the hypothesis that MGMT is regulated by p53 in astrocytic cells,...

Background & Objective: Papillary thyroid cancer (PTC) is considered to be the most common type of thyroid malignancies. Epigenetic alteration, in which the chromatin conformation and gene expression change without changing the sequence of DNA, can occur in some tumor suppressor genes and oncogenes. Methylation is the most common type of epigenetic alterations that can be an ex...

BACKGROUND Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. We aimed to explore the methylation status of MGMT gene among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is high. MATERIALS AND METH...

BACKGROUND Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial c...

We observed previously that wild-type p53 rendered neonatal mouse astrocytes resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in a gene dose-dependent fashion. This effect of p53 appeared to be unrelated to its cell cycle regulation or apoptotic functions. Because in many cell types O(6)-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair is an important mechanism of resistan...