MC13-0089 Epigenome-wide discovery of ovarian and breast cancer specific DNA methylation markers

Background: Breast and ovarian cancers pose huge and unsolved challenges to the medical profession. Breast cancer is the most common cancer in women in the EU: more than 332,000 women are diagnosed with breast cancer each year and a woman dies every 6 minutes from this disease. Ovarian cancer, whilst far less common than breast cancer, is often diagnosed when the disease is at an advanced stage and has spread to other areas of the body. More than 60% of ovarian cancer patients die within the first 5 years after diagnosis. Implementation of successful screening programs has dramatically reduced the number of women dying from cervical cancer. Similarly, the EU FP7 consortium EpiFemCare aims to reduce the number of women diagnosed with late stage breast or ovarian cancer by 50%, reduce the number of women who receive unnecessary long-term chemotherapy by 50%, and reduce the number of women dying from these cancers by 20%. Purpose/Objective: EpiFemCare will establish and clinically validate a series of blood tests based upon DNA methylation technology that will facilitate both early detection and prediction of therapeutic outcome. The project consists of three phases: (1) Epigenome-wide discovery of ovarian/breast cancer specific DNA methylation markers. (2) Development of serum based assays for cancer specific markers. (3) Validation of the serum test performance in thousands of serial samples from prospective clinical trials. Materials and Methods: In phase 1 Illumina Infinium Human Methylation450 BeadChip Array technology is used to assess the methylation status of ∼485,000 sites in cancer and control tissues. In parallel Reduced Representation Bisulfite Sequencing (RRBS) is used to identify & confirm cancer specific methylated circulating DNA in matching serum samples. Results: Using Genedata Expressionist® for Genomic Profiling, we have established an automated bioinformatics pipeline for the detection of cancer specific differentially methylated regions (DMRs) that are most likely to fulfill the strict specificity criteria of a serum based test. Conclusions: The most promising DMRs are taken forward for the serum based clinical assay development and validation.