MGMT (O^6^-methylguanine-DNA methyltransferase) is a DNA repair enzyme that plays a crucial role in protecting the genome from alkylating damage. Key points include:
-MGMT repairs DNA lesions by removing alkyl groups from the O^6^-position of guanine, thereby preventing mutations.
-It is a “suicide enzyme,” meaning that it is inactivated after repairing one lesion.
-By counteracting the cytotoxic effects of alkylating agents, MGMT is a critical determinant of cell survival following exposure to such chemotherapeutic agents.
In several cancers, the MGMT promoter is hypermethylated. This epigenetic modification suppresses MGMT expression and has several implications:
-Reduced MGMT levels lead to an accumulation of DNA damage.
-Increased mutation rates can contribute to cancer initiation and progression.
MGMT expression levels in tumors have a significant impact on the response to alkylating agents (e.g., temozolomide in glioblastoma).
-High MGMT Expression: Can confer resistance to these drugs by effectively repairing the induced DNA damage.
-Low MGMT Expression: Often observed in tumors with MGMT promoter hypermethylation, making the cancer cells more susceptible to chemotherapeutic agents.
Improved Prognosis with Low MGMT Expression in Specific Contexts (high MGMT activity can allow tumor cells to recover from DNA damage).
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