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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.

Publication ,  Journal Article
Smith, IM; Glazer, CA; Mithani, SK; Ochs, MF; Sun, W; Bhan, S; Vostrov, A; Abdullaev, Z; Lobanenkov, V; Gray, A; Liu, C; Chang, SS; Begum, S ...
Published in: PLoS One
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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2009

Volume

4

Issue

3

Start / End Page

e4961

Location

United States

Related Subject Headings

  • Transketolase
  • Proto-Oncogenes
  • Proto-Oncogene Mas
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Microarray Analysis
  • Lung Neoplasms
  • Humans
  • Head and Neck Neoplasms
  • General Science & Technology
 

Citation

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Smith, I. M., Glazer, C. A., Mithani, S. K., Ochs, M. F., Sun, W., Bhan, S., … Califano, J. (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), e4961. https://doi.org/10.1371/journal.pone.0004961
Smith, Ian M., Chad A. Glazer, Suhail K. Mithani, Michael F. Ochs, Wenyue Sun, Sheetal Bhan, Alexander Vostrov, et al. “Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.PLoS One 4, no. 3 (2009): e4961. https://doi.org/10.1371/journal.pone.0004961.
Smith, Ian M., et al. “Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.PLoS One, vol. 4, no. 3, 2009, p. e4961. Pubmed, doi:10.1371/journal.pone.0004961.
Smith IM, Glazer CA, Mithani SK, Ochs MF, Sun W, Bhan S, Vostrov A, Abdullaev Z, Lobanenkov V, Gray A, Liu C, Chang SS, Ostrow KL, Westra WH, Begum S, Dhara M, Califano J. Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer. PLoS One. 2009;4(3):e4961.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2009

Volume

4

Issue

3

Start / End Page

e4961

Location

United States

Related Subject Headings

  • Transketolase
  • Proto-Oncogenes
  • Proto-Oncogene Mas
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Microarray Analysis
  • Lung Neoplasms
  • Humans
  • Head and Neck Neoplasms
  • General Science & Technology