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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.

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Date
2009
Authors
Smith, Ian M
Glazer, Chad A
Mithani, Suhail K
Ochs, Michael F
Sun, Wenyue
Bhan, Sheetal
Vostrov, Alexander
Abdullaev, Ziedulla
Lobanenkov, Victor
Gray, Andrew
Liu, Chunyan
Chang, Steven S
Ostrow, Kimberly L
Westra, William H
Begum, Shahnaz
Dhara, Mousumi
Califano, Joseph
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(17 total)
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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 article
Subject
Animals
Antigens, 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
Permalink
https://hdl.handle.net/10161/10198
Published Version (Please cite this version)
10.1371/journal.pone.0004961
Publication 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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Scholars@Duke

Mithani

Suhail Kamrudin Mithani

Associate Professor of Surgery
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