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

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.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18091988
DOI: 10.1371/journal.pone.0001314

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 ( approximately 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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics
CSHL Authors:
Communities: CSHL labs > Martienssen lab
Depositing User: CSHL Librarian
Date Deposited: 07 Nov 2011 20:05
Last Modified: 09 Apr 2014 20:19
PMCID: PMC2117343
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23113

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