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Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.

dc.contributor.author Smith, IM
dc.contributor.author Glazer, CA
dc.contributor.author Mithani, SK
dc.contributor.author Ochs, MF
dc.contributor.author Sun, W
dc.contributor.author Bhan, S
dc.contributor.author Vostrov, A
dc.contributor.author Abdullaev, Z
dc.contributor.author Lobanenkov, V
dc.contributor.author Gray, A
dc.contributor.author Liu, C
dc.contributor.author Chang, SS
dc.contributor.author Ostrow, KL
dc.contributor.author Westra, WH
dc.contributor.author Begum, S
dc.contributor.author Dhara, M
dc.contributor.author Califano, J
dc.coverage.spatial United States
dc.date.accessioned 2015-05-28T18:38:20Z
dc.date.issued 2009
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/19305507
dc.identifier.uri https://hdl.handle.net/10161/10198
dc.description.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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
dc.language eng
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0004961
dc.subject Animals
dc.subject Antigens, Neoplasm
dc.subject Base Sequence
dc.subject Cell Line, Tumor
dc.subject DNA Methylation
dc.subject DNA-Binding Proteins
dc.subject Epigenesis, Genetic
dc.subject Gene Expression Profiling
dc.subject Gene Expression Regulation, Neoplastic
dc.subject Head and Neck Neoplasms
dc.subject Humans
dc.subject Lung Neoplasms
dc.subject Microarray Analysis
dc.subject Molecular Sequence Data
dc.subject Promoter Regions, Genetic
dc.subject Proto-Oncogenes
dc.subject Transketolase
dc.title Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/19305507
pubs.begin-page e4961
pubs.issue 3
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Orthopaedics
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Plastic, Maxillofacial, and Oral Surgery
pubs.publication-status Published
pubs.volume 4
dc.identifier.eissn 1932-6203


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