title: MGMT promoter methylation status in Merkel cell carcinoma: in vitro versus invivo.
abstract: OBJECTIVE
  Expression of O6-methylguanine-DNA methyltransferase (MGMT) in Merkel cell carcinoma (MCC) is very variable; thus, we tested whether this may be due to differential methylation of the MGMT gene promoter.
  
  
  METHODS
  Quantitative analysis of MGMT mRNA and protein expression, as well as MGMT promoter methylation status, was performed in a series of tissue samples of MCC tumors, representing both primary and metastatic lesions, as well as in six MCC cell lines.
  
  
  RESULTS
  These analyses revealed a very heterogeneous MGMT mRNA and protein expression in MCC both in vivo and in vitro. However, neither the MGMT mRNA nor protein expression correlated with the sensitivity of MCC cell lines toward the alkylating agent dacarbazine in vitro. Notably, increased methylation at the promoter of the MGMT gene was observed in 2/6 (33%) of the MCC cell lines; however, MGMT promoter methylation was absent in all MCC tissue samples. According to our results, albeit aberrant methylation of MGMT gene promoter can be observed in in vitro propagated MCC cell lines, it seems to be absent or very rare in MCC lesions in situ.
  
  
  CONCLUSIONS
  Thus, the evaluation of this marker has no or only little significance for predicting response to therapy or for improving efficacy of demethylating agents in the treatment of MCC. Microenvironmental factors may play a role in explaining the different results between MCC cell lines and MCC samples.
authors.affiliation: Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Rionero in Vulture, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Improta
authors.affiliation: Department of Translational Skin Cancer Research (tscr), University Hospital Essen, Universitätstraße 1, 45141, Essen, Germany.|German Cancer Consortium (DKTK), Essen, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Ritter
authors.affiliation: Department of Pathology, Azienda Ospedaliera per l' Emergenza Cannizzaro, Catania, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Pettinato
authors.affiliation: Department of Pathology, Azienda Ospedaliera per l' Emergenza Cannizzaro, Catania, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Vasta
authors.affiliation: Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.affiliation: Department of Pathology, Azienda Ospedaliera per l' Emergenza Cannizzaro, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Fraggetta
authors.affiliation: Department of Translational Skin Cancer Research (tscr), University Hospital Essen, Universitätstraße 1, 45141, Essen, Germany. j.becker@dkfz-heidelberg.de.|German Cancer Consortium (DKTK), Essen, Germany. j.becker@dkfz-heidelberg.de.|German Cancer Research Center (DKFZ), Heidelberg, Germany. j.becker@dkfz-heidelberg.de.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D015266:Carcinoma, Merkel Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: Epigenetic regulation; MGMT gene promoter; Merkel cell carcinoma; Methylation status