title: Abnormal methylation of histone deacetylase genes: implications on etiology and epigenetic therapy of astrocytomas.
abstract: BACKGROUND
  A growing body of evidence has revealed the involvement of epigenetic alterations in the etiology of astrocytomas. In the present study, we aimed to evaluate the association of DNA methylation of histone deacetylase genes (HDAC) with the etiology of astrocytoma, and the implications for epigenetic therapy.
  
  
  METHODS
  Methylation of the HDAC4, HDAC5 and HDAC6 genes was assessed in 29 tumor samples (astrocytomas grades I, III, and IV) and in the glioblastoma cell lines U87, U251, U343, SF188, and T98G by methylation-specific quantitative PCR (MSED-qPCR).
  
  
  RESULTS
  Significantly increased methylation of the HDAC5 gene was observed in astrocytomas when compared to non-neoplastic brain samples (p=0.0007) and to glioblastomas cell lines (p=0.001). A heterogenic methylation pattern was evidenced when compared to the glioblastoma cell lines. Distinct effects on methylation and gene expression were observed after in vitro treatment of the different cell lines with decitabine.
  
  
  CONCLUSIONS
  Our results suggest that abnormal methylation of HDAC genes is involved in the etiology of astrocytomas and indicate that loci-specific epigenetic interindividualities might be associated to the differential responses to treatment with decitabine.
authors.affiliation: Centre of Biological and Health Sciences, University of Northern Paraná, PR, Brazil. mvmgomes@gmail.com
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomes
authors.forename: Kleiton Silva
authors.initials: KS
authors.lastname: Borges
authors.forename: Daniel Antunes
authors.initials: DA
authors.lastname: Moreno
authors.forename: Rosane Gomes
authors.initials: RG
authors.lastname: Queiroz
authors.forename: Hélio Rubens
authors.initials: HR
authors.lastname: Machado
authors.forename: Carlos Gilberto
authors.initials: CG
authors.lastname: Carlotti
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Scrideli
authors.forename: Luiz Gonzaga
authors.initials: LG
authors.lastname: Tone
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001254:Astrocytoma / Q000188:drug therapy / Q000209:etiology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000209:etiology*; D002648:Child; D003114:Colony-Forming Units Assay; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D000077209:Decitabine; D044127:Epigenesis, Genetic; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D012097:Repressor Proteins; D000077209:Decitabine; C400300:HDAC4 protein, human; C404500:HDAC5 protein, human; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D001374:Azacitidine