lomeguatrib and Hodgkin-Disease

We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter and mRNA expression in HL cells and assessed the response of these cells to dacarbazine. Expression of MGMT correlated with the presence of non-methylated promoters and cell lines with non-methylated promoters showed increased resistance against dacarbazine. KM-H2 cells expressed fusion transcripts between MGMT and proline-rich coiled-coil 2B (PRRC2B) but no wild type MGMT transcripts. Dacarbazine sensitivity suggested that fusion transcripts are translated into a protein with reduced functionality. MGMT promoter methylation predicts dacarbazine sensitivity of HL cells and it might be interesting to analyze this factor in HL patients.

Topics: Antineoplastic Agents, Alkylating; Azacitidine; Cell Line, Tumor; Cell Survival; Dacarbazine; DNA Methylation; Drug Resistance, Neoplasm; Drug Synergism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Hodgkin Disease; Humans; Immunoblotting; O(6)-Methylguanine-DNA Methyltransferase; Promoter Regions, Genetic; Purines; Reverse Transcriptase Polymerase Chain Reaction