title: Impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine resistance of Hodgkin's lymphoma cells.
abstract: 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.
authors.affiliation: Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kewitz
authors.affiliation: Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Stiefel
authors.affiliation: Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Christof M
authors.initials: CM
authors.lastname: Kramm
authors.affiliation: Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany. Electronic address: martin.staege@medizin.uni-halle.de.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Staege
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation; D003606:Dacarbazine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011687:Purines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011687:Purines; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D001374:Azacitidine; C521206:lomeguatrib
keywords: Dacarbazine; Hodgkin's lymphoma; O6-methylguanine-DNA methyltransferase; Promoter methylation