title: Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.
abstract: BACKGROUND
  Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC.
  
  
  RESULTS
  We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells.
  
  
  CONCLUSIONS
  Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Smith
authors.forename: Chad A
authors.initials: CA
authors.lastname: Glazer
authors.forename: Suhail K
authors.initials: SK
authors.lastname: Mithani
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ochs
authors.forename: Wenyue
authors.initials: W
authors.lastname: Sun
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bhan
authors.forename: Alexander
authors.initials: A
authors.lastname: Vostrov
authors.forename: Ziedulla
authors.initials: Z
authors.lastname: Abdullaev
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: Andrew
authors.initials: A
authors.lastname: Gray
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.forename: Steven S
authors.initials: SS
authors.lastname: Chang
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Ostrow
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Begum
authors.forename: Mousumi
authors.initials: M
authors.lastname: Dhara
authors.forename: Joseph
authors.initials: J
authors.lastname: Califano
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014174:Transketolase / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C505431:TKTL1 protein, human; D014174:Transketolase