Abstract
Cancer has long been considered a genetic disease, characterized by a sequential accumulation of genetic alterations. Growing evidence indicates that epigenetic alterations add an additional layer of complexity to the pathogenesis of cancer, and may characterize subgroups of cancer with a distinct etiology and prognosis. Epigenetic dysregulation in cancer is organized at multiple levels, involving amongst others DNA methylation. Aberrant promoter methylation is involved in transcriptional silencing of tumor suppressor and DNA repair genes. We have used multiple strategies to identify epigenetically inactivated tumor suppressor genes and DNA repair genes in cancer. These epigenetic screens have provided (1) novel insight in the biology of cancer and (2) novel methylation markers for early detection of cancer and the prediction of prognosis and response to therapy. Before these markers can be used in the clinic they have to be validated in large, well characterized population-based cohorts and randomized clinical trials and evaluated for efficacy and costeffectiveness against the current gold standards. Here we present the identification of novel methylation markers for colorectal and renal cell cancer, including evidence for a tumor suppressor function of the genes involved and their application as biomarkers. STROMAL AND EPITHELIAL CELLS OF ENDOMETRIOSIS FROM DIFFERENT ANATOMICAL SITES SHARE THE SAME GENOMIC IMBALANCES, SUGGESTING A COMMON ORIGIN
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