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MGMT Methylated. MGMT methylated is when the genetics responsible for a type of brain tumor called a glioblastoma have been altered by a chemical process called methylation. A MGMT methylated glioblastoma allows for a better patient response to treatments, specifically temozolomide and radiation.
Targeted epigenetic editing as novel therapy for malignant glioma
Malignant glioma has a poor prognosis, despite current therapeutic modalities. Standard of care therapy consists of surgical resection, fractionated radiotherapy concurrently administered with temozolomide (TMZ), a DNA-alkylating chemotherapeutic agent, followed by adjuvant cycles of TMZ. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme which removes alkylated lesions from tumor DNA, thereby promoting chemoresistance. MGMT promoter methylation is a known predictor of temozolomide responsiveness; patients with unmethylated MGMT have a poorer prognosis. We employed deactivated Cas9-CRISPR technology to effectively target methylation in the vicinity of the MGMT methylation-specific polymerase chain reaction (MSP) region, as mediated by the catalytic domain of DNA methyltransferase DNMT3A. In doing so, we discovered that the selected dCas9 / CRISPR-mediated methylation of certain regions of MGMT gene sequences can be used to enhance chemosensitivity in malignant glioma cells.
Owner:RGT UNIV OF CALIFORNIA