MGMT Testing

MGMT Testing

MGMT Testing

MGMT is an enzyme found in many normal tissues, including brain. It is responsible for ensuring the quality of cellular DNA, by repairing specific types of DNA injury.

Because cancer cells may acquire a selective advantage through allowing some level of DNA injury (thereby generating further mutants which can avoid host defenses or cancer treatments), many cancers fail to express MGMT.

Several of the common treatments for gliomas, including alkylating agents such as temozolamide and carmustine, kill cancer cells by causing selective damage to tumor DNA. If the tumor is one which expresses MGMT, this damage may be undone, and the treatment will then be less effective or completely ineffective.

Two general techniques have been used to determine whether cells of tumors such as gliomas can express MGMT. Using specific antibodies, the presence of MGMT protein in tumor cells can be assessed directly by immunohistochemistry (IHC).

Alternatively, the part of the MGMT gene which controls whether the protein is made or not, the gene promoter, may be modified in a way (usually by methylation of cytosine residues) which prevents MGMT protein from being expressed.

Numerous studies have shown that brain tumors lacking MGMT (either by IHC or by assessing promoter methylation) respond better to chemotherapy than those expressing MGMT. As shown in a recent paper by Esteller & colleagues, the differences can be quite dramatic, with MGMT-negative tumors surviving, on average, a year longer than those that were MGMT-positive.

TissuPath's Division of Neuropathology, in collaboration with the Peter MacCallum Cancer Centre, tests for MGMT by assessing both promoter methylation and protein expression by immunohistochemistry.

To request testing, contact A/Prof Michael Gonzales,
E: <m.gonzales@tissupath.com>
C: 0408 571 359
V: 9815-1588

Testing requires formalin-fixed, paraffin-embedded tissue blocks of the tumor for review and DNA extraction from representative areas of the tumor. Results are usually available within 2-3 weeks. As the test is not on the Medicare list, the cost ($525) must be billed to either the patient or the referring institution.