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. 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.
Type
Journal articleSubject
AnimalsAntigens, Neoplasm
Base Sequence
Cell Line, Tumor
DNA Methylation
DNA-Binding Proteins
Epigenesis, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
Humans
Lung Neoplasms
Microarray Analysis
Molecular Sequence Data
Promoter Regions, Genetic
Proto-Oncogenes
Transketolase
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https://hdl.handle.net/10161/10198Published Version (Please cite this version)
10.1371/journal.pone.0004961Publication Info
Smith, Ian M; Glazer, Chad A; Mithani, Suhail K; Ochs, Michael F; Sun, Wenyue; Bhan,
Sheetal; ... Califano, Joseph (2009). Coordinated activation of candidate proto-oncogenes and cancer testes antigens via
promoter demethylation in head and neck cancer and lung cancer. PLoS One, 4(3). pp. e4961. 10.1371/journal.pone.0004961. Retrieved from https://hdl.handle.net/10161/10198.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Suhail Kamrudin Mithani
Associate Professor of Surgery

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