CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 (MLH1) and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present stud...

Defects in DNA repair may be responsible for the genesis of mutations in key genes in cancer cells. The tumor suppressor gene p53 is commonly mutated in human cancer by missense point mutations, most of them G:C to A:T transitions. A recognized cause for this type of change is spontaneous deamination of the methylcytosine. However, the persistence of a premutagenic O(6)-methylguanine can also b...

O(6)-Methylguanine and O(6)-chloroethylguanine, which are the primary cytotoxic DNA lesions produced by 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (dacarbazine) and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), respectively, can be repaired by O(6)-methylguanine-DNA methyltransferase (MGMT), coded by the MGMT gene. However, the two types of drugs exhib...

PURPOSE To investigate the role of epigenetic changes in the promoter region of tumor-suppressor genes in the retinoblastoma genome and to study the disruption of expression of O6-methylguanine-DNA Methyltransferase (MGMT) due to aberrant methylation and its association with retinoblastoma. METHODS A series of 23 retinoblastoma tissue specimens and 2 retinoblastoma cell lines (Y79 and WERI-Rb...

BACKGROUND Resistance to temozolomide (TMZ) in glioma is modulated by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). This study aimed to examine the effects of fluoxetine (FLT) on MGMT expression in glioma cells and to investigate its underlying mechanisms. MATERIALS AND METHODS Expression of MGMT, GluR1, or IκB kinase β (IKKβ) was attenuated using short hairpin RNA-med...

Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are strongly associated with epigenetic silencing of the methylguanine DNA methyltransferase (MGMT) gene. However, little is known about the percentage of MGMT-methyl...

Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O(6)-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher's exact test. Some BTICs were sensitive. Sen...

The mechanism whereby the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is silenced in repair-deficient (Mer-) human tumor cells is unknown. The role of methylation of the 5' CpG island in MGMT gene suppression is controversial. Although we previously showed by restriction enzyme analysis that CpG methylation in this region was associated with gene suppression, methylation at...

O-6-methylguanine-DNA methyltransferase (MGMT) has been associated with resistance to alkylating agent cancer therapy in Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults. Lower expression or silencing of the MGMT protein by promoter methylation has been reported to improve survival in patients with GBM [1]. This protocol describes bisulfite conversion, methylatio...

Chloroethylnitrosoureas (CNUs) are being used in the therapy of various neoplastic diseases, including skin cancer. Because secondary tumor formation is a serious threat in chemotherapy with these drugs, we explored whether and to what extent the DNA repair protein DNA-O6-methylguanine:protein-L-cysteine S-methyltransferase (MGMT) protects against CNU-induced tumors. We made use of transgenic m...