title: Epigenetic repression of HOXB cluster in oral cancer cell lines.
abstract: OBJECTIVE
  Aberrant DNA methylation is a fundamental transcriptional control mechanism in carcinogenesis. The expression of homeobox genes is usually controlled by an epigenetic mechanism, such as the methylation of CpG islands in the promoter region. The aim of this study was to describe the differential methylation pattern of HOX genes in oral squamous cell carcinoma (OSCC) cell lines and transcript status in a group of hypermethylated and hypomethylated genes.
  
  
  METHODS
  Quantitative analysis of DNA methylation was performed on two OSCC cell lines (SCC4 and SCC9) using a method denominated Human Homeobox Genes EpiTect Methyl qPCR Arrays, which allowed fast, precise methylation detection of 24 HOX specific genes without bisulfite conversion.
  
  
  RESULTS
  Methylation greater than 50% was detected in HOXA11, HOXA6, HOXA7, HOXA9, HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXC8 and HOXD10. Both cell lines demonstrated similar hypermethylation status for eight HOX genes. A similar pattern of promoter hypermethylation and hypomethylation was demonstrated for the HOXB cluster and HOXA cluster, respectively. Moreover, the hypermethylation profile of the HOXB cluster, especially HOXB4, was correlated with decreased transcript expression, which was restored following treatment with 5-aza-2'-deoxycytidine.
  
  
  CONCLUSIONS
  The homeobox methylation profile in OSCC cell lines is consistent with an epigenetic biomarker.
authors.affiliation: Department of Propaedeutics and Integrated Clinic, School of Dentistry, Federal University of Bahia, Av. Araujo Pinho, 62, Canela, Salvador 40110-150 Bahia, Brazil.
authors.forename: Flávia Caló Aquino
authors.initials: FC
authors.lastname: Xavier
authors.affiliation: Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, Butantã São Paulo, 05508-000 Brazil.
authors.forename: Maria Fernanda de Souza Setubal
authors.initials: MF
authors.lastname: Destro
authors.affiliation: Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, Butantã São Paulo, 05508-000 Brazil.
authors.forename: Carina Magalhães Esteves
authors.initials: CM
authors.lastname: Duarte
authors.affiliation: Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, Butantã São Paulo, 05508-000 Brazil. Electronic address: fadnunes@usp.br.
authors.forename: Fabio Daumas
authors.initials: FD
authors.lastname: Nunes
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D063185:Epigenetic Repression; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000077209:Decitabine; D001374:Azacitidine
keywords: DNA methylation; Epigenetics; HOX genes; Oral cancer