Discovery of Novel DNA Methylation Biomarker of Ovarian Cancer Using New Generation Sequencing Technology

Ovarian cancer is the most lethal cancer in gynecologic malignancies. The etiology is unknown and the poor outcome has been persistent for decades. Although, the therapeutic responses are individualized, all patients are treated by the same way. There is an urgent need of biomarkers for the stratification of ovarian cancer patients for personalized medicine. In addition, the therapeutic outcome of early stage ovarian cancer is excellent. However, there are no satisfactory methods yet. The development of effective methods of early detection of ovarian cancer is also needed. Epigenetic alterations have been shown to occur in many types of cancer. Decades of researches have demonstrated the potential of DNA methylation as a marker for early diagnosis of cancer and as a means of assessing the prognosis of cancer patients. Mapping of genome-wide methylation could leads to discover novel genes for disease diagnosis and treatment responsiveness. The genome-wide DNA methylation analysis in ovarian tumors has yet to be explored extensively. The present study is to use methyl-DNA capture coupled with new generation sequencing to discover novel DNA methylation biomarkers for ovarian cancer prognosis prediction and detection. We will analyze 100 benign and malignant ovarian tumors and compare the methylomic profiles using various bioinformatics. Potential loci will be validated by pyrosequencing and quantitative methylation-specific PCR. Testing will be done using tumor tissues and serum/plasma to verify the clinical potential. Novel genes will be subjected to functional analysis. These studies may not only discover new biomarkers but also lead to novel therapeutics. The progress of the first 2 years is a little bit ahead of schedule. This part is the 3rd part of the 3-year project focusing on the development of DNA methylation detetion from blood and functional characterizations of novel genes with clinical application potential.