Identification of novel high-frequency DNA methylation changes in breast cancer

Jared M. Ordway, Muhammad A. Budiman, Yulia Korshunova, Rebecca K. Maloney, Joseph A. Bedell, Robert W. Citek, Blaire Bacher, Seth Peterson, Tracy Rohlfing, Jacqueline Hall, Robert Brown, Nathan Lakey, Rebecca W. Doerge, Robert A. Martienssen, Jorge Leon, John Douglas Mcpherson, Jeffrey A. Jeddeloh

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Recent data have revealed that epigenetic alterations, including DNA methylation and chromatin structure changes, are among the earliest molecular abnormalities to occur during tumorigenesis. The inherent thermodynamic stability of cytosine methylation and the apparent high specificity of the alterations for disease may accelerate the development of powerful molecular diagnostics for cancer. We report a genome-wide analysis of DNA methylation alterations in breast cancer. The approach efficiently identified a large collection of novel differentially DNA methylated loci (∼200), a subset of which was independently validated across a panel of over 230 clinical samples. The differential cytosine methylation events were independent of patient age, tumor stage, estrogen receptor status or family history of breast cancer. The power of the global approach for discovery is underscored by the identification of a single differentially methylated locus, associated with the GHSR gene, capable of distinguishing infiltrating ductal breast carcinoma from normal and benign breast tissues with a sensitivity and specificity of 90% and 96%, respectively. Notably, the frequency of these molecular abnormalities in breast tumors substantially exceeds the frequency of any other single genetic or epigenetic change reported to date. The discovery of over 50 novel DNA methylation-based biomarkers of breast cancer may provide new routes for development of DNA methylation-based diagnostics and prognostics, as well as reveal epigenetically regulated mechanism involved in breast tumorigenesis.

Original languageEnglish (US)
Article numbere1314
JournalPLoS One
Volume2
Issue number12
DOIs
StatePublished - Dec 19 2007
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    Ordway, J. M., Budiman, M. A., Korshunova, Y., Maloney, R. K., Bedell, J. A., Citek, R. W., Bacher, B., Peterson, S., Rohlfing, T., Hall, J., Brown, R., Lakey, N., Doerge, R. W., Martienssen, R. A., Leon, J., Mcpherson, J. D., & Jeddeloh, J. A. (2007). Identification of novel high-frequency DNA methylation changes in breast cancer. PLoS One, 2(12), [e1314]. https://doi.org/10.1371/journal.pone.0001314