Detection of O6-methylguanine-DNA methyltransferase-expression in human tumors by means of in situ hybridization.

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a main determinant of resistance of tumor cells towards nitrosoureas that are in use as cytostatic drugs. It therefore appears of importance to determine its expression in tumors before the utilization of nitrosoureas for tumor treatment. We have determined the level of expression of MGMT in mammary carcinomas and brain tumors by means of in situ hybridization, using digoxygenin-labeled RNA driven by MGMT expression vector in sense and antisense orientation. It is shown that the intensity of the hybridization signal correlates with the MGMT activity of a given tumor. The results demonstrate the applicability of in situ hybridization for determination of MGMT expression in tumor sections.