Epigenetic Characterization of Ovarian Cancer
Final rept. 15 Nov 2004-14 Nov 2008
DUKE UNIV MEDICAL CENTER DURHAM NC
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The overall objective of this research was to identify genes that are aberrantly methylated in epithelial ovarian cancer. Our approach was to treat or mock treat primary normal or tumor cultured cells with drugs that inhibit DNA methyltransferase activity and then perform microarray analysis to identify genes that are likely to exhibit methylation-mediated silencing. We also employed similar analysis of 43 ovarian cell lines. Two major criteria identified genes likely to be methylated maximum fold-change in expression following drug treatment, and a high standard deviation in expression among untreated cells. These criteria were validated using a gene set known to exhibit methylation in other cancers and led to prediction of a total of 360 methylated genes in ovarian cancer, among which 32 were validated. Genes involved in TGF-beta pathway activity were overrepresented among the candidates, and their methylation status was confirmed. Pathway activity was found to increase when DNA methyltransferase activity is inhibited, indicating coordinate epigenetic suppression of this pathway in ovarian cancer.
- Genetic Engineering and Molecular Biology
- Organic Chemistry