Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

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 naive 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. (J Mol Diagn 2009 11:60-65; DOI: 10.2353/jmoldx.2009.080072)