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Originally published online as doi:10.2353/jmoldx.2009.080072 on December 12, 2008

Published online before print December 12, 2008
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Journal of Molecular Diagnostics 2009, Vol. 11, No. 1
Copyright © 2009 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2009.080072

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

Anatoliy Melnikov*, Denise Scholtens*{dagger}, Andrew Godwin{ddagger} and Victor Levenson*

From the Robert H. Lurie Comprehensive Cancer Center, * and the Department of Preventive Medicine, {dagger} Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and the Fox Chase Cancer Center, {ddagger} Department of Medical Oncology, Philadelphia, Pennsylvania

An accurate biomarker for detection of ovarian cancer may reduce cancer-related mortality. Using a previously developed microarray-based technique, we evaluated differences in DNA methylation profiles in a panel of 56 genes using sections of serous papillary adenocarcinomas and uninvolved ovaries (n = 30) from women in a high-risk group. Methylation profiles were also generated for circulating DNA from blood of patients (n = 33) and healthy controls (n = 33). Using the most differentially methylated genes for naïve Bayesian analysis, we identified ten of these profiles as potentially informative in tissues. Various combinations of these genes produced 69% sensitivity and 70% specificity for cancer detection as estimated under a stratified, fivefold cross-validation protocol. In plasma, five genes were identified as informative; their combination had 85% sensitivity and 61% specificity for cancer detection. These results suggest that differential methylation profiling in heterogeneous samples has the potential to identify components of a composite biomarker that may detect ovarian cancer in blood with significant accuracy.






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Copyright © 2009 by the American Society for Investigative Pathology and the Association for Molecular Pathology.