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

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

United States

2015-05-28T18:38:20Z

2009

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.

https://www.ncbi.nlm.nih.gov/pubmed/19305507

1932-6203

https://hdl.handle.net/10161/10198

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0004961

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

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

Journal article

Mithani, Suhail K|0000-0002-3762-0831

https://www.ncbi.nlm.nih.gov/pubmed/19305507

e4961

3

Clinical Science Departments

Duke

Orthopaedics

School of Medicine

Surgery

Surgery, Plastic, Maxillofacial, and Oral Surgery

Published

4