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Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer.

Publication ,  Journal Article
Matsumura, N; Huang, Z; Mori, S; Baba, T; Fujii, S; Konishi, I; Iversen, ES; Berchuck, A; Murphy, SK
Published in: Genome Res
January 2011

Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. Diagnosis usually occurs after metastatic spread, largely reflecting vague symptoms of early disease combined with lack of an effective screening strategy. Epigenetic mechanisms of gene regulation, including DNA methylation, are fundamental to normal cellular function and also play a major role in carcinogenesis. To elucidate the biological and clinical relevance of DNA methylation in ovarian cancer, we conducted expression microarray analysis of 39 cell lines and 17 primary culture specimens grown in the presence or absence of DNA methyltransferase (DNMT) inhibitors. Two parameters, induction of expression and standard deviation among untreated samples, identified 378 candidate methylated genes, many relevant to TGF-beta signaling. We analyzed 43 of these genes and they all exhibited methylation. Treatment with DNMT inhibitors increased TGF-beta pathway activity. Hierarchical clustering of ovarian cancers using the 378 genes reproducibly generated a distinct gene cluster strongly correlated with TGF-beta pathway activity that discriminates patients based on age. These data suggest that accumulation of age-related epigenetic modifications leads to suppression of TGF-beta signaling and contributes to ovarian carcinogenesis.

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Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

January 2011

Volume

21

Issue

1

Start / End Page

74 / 82

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Signal Transduction
  • Ovarian Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Neoplasms, Glandular and Epithelial
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female
 

Citation

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Matsumura, N., Huang, Z., Mori, S., Baba, T., Fujii, S., Konishi, I., … Murphy, S. K. (2011). Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer. Genome Res, 21(1), 74–82. https://doi.org/10.1101/gr.108803.110
Matsumura, Noriomi, Zhiqing Huang, Seiichi Mori, Tsukasa Baba, Shingo Fujii, Ikuo Konishi, Edwin S. Iversen, Andrew Berchuck, and Susan K. Murphy. “Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer.Genome Res 21, no. 1 (January 2011): 74–82. https://doi.org/10.1101/gr.108803.110.
Matsumura N, Huang Z, Mori S, Baba T, Fujii S, Konishi I, et al. Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer. Genome Res. 2011 Jan;21(1):74–82.
Matsumura, Noriomi, et al. “Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer.Genome Res, vol. 21, no. 1, Jan. 2011, pp. 74–82. Pubmed, doi:10.1101/gr.108803.110.
Matsumura N, Huang Z, Mori S, Baba T, Fujii S, Konishi I, Iversen ES, Berchuck A, Murphy SK. Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer. Genome Res. 2011 Jan;21(1):74–82.

Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

January 2011

Volume

21

Issue

1

Start / End Page

74 / 82

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Signal Transduction
  • Ovarian Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Neoplasms, Glandular and Epithelial
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female