Accession Number : ADA509791


Title :   Epigenetic Characterization of Ovarian Cancer


Descriptive Note : Final rept. 15 Nov 2004-14 Nov 2008


Corporate Author : DUKE UNIV MEDICAL CENTER DURHAM NC


Personal Author(s) : Murphy, Susan K


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a509791.pdf


Report Date : Dec 2008


Pagination or Media Count : 105


Abstract : 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.


Descriptors :   *OVARIAN CANCER , *GENES , *IDENTIFICATION , *METHYLATION , *DEOXYRIBONUCLEIC ACIDS , COMPUTATIONAL CHEMISTRY , TRANSFERASES , OVARIES , CELLS(BIOLOGY) , VALIDATION , EPITHELIUM , INHIBITORS


Subject Categories : Genetic Engineering and Molecular Biology
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE