MGMT is a DNA repair enzyme that participates in a suicide reaction that specifically removes methyl or alkyl groups from the O(6) position of guanine, restoring guanine to its normal form without causing DNA breaks. MGMT protects cells from alkylating toxins, and is an important factor in drug resistance to alkylating therapeutic agents. It is ubiquitously expressed in normal human tissues and is overexpressed in many types of human tumors, but epigenetically silenced in other tumors. MGMT silencing is a marker associated with poor prognosis, but is a good predictive marker for response to alkylating agent chemotherapy.
[1] Pegg, A.E. (2000) Mutat. Res. 462, 83-100.
[2] Bobola, M.S. et al. (2005) Clin. Cancer Res. 11, 2747-2755.
[3] Pollack, I.F. et al. (2006) J. Clin. Oncol. 24, 3431-3437.
[4] Gerson, S.L. et al. (1986) Carcinogenesis 7, 745-749.
[5] Soejima, H. et al. (2005) Biochem. Cell Biol. 83, 429-437.
