EPIDIACAN · Development of sensitive methodologies for exploitation of early epigenetic marker diagnosis in major types of cancer

Cancer is one of the major causes of mortality. Epithelial cells become malignant after accumulating genetic mutations followed by morphological changes in the epithelium. DNA Alterations include stable genetic changes in oncogenes, tumor suppressor genes and reversible epigenetic changes. Different forms of epigenetic mechanisms have been shown to modify the expression of key genes during tumour progression. Promoter DNA hypermethylation of tumour suppressor genes or DNA repair genes, and covalent histone modifications appear in early stages of neoplasia. Methods to identify early markers in different types of cancer are being developed, although very few are specific and sensitive enough to be applied in the clinic. The aim of the present proposal is to develop sensitive and specific methodologies to identify early epigenetic markers for major types of cancer, like prostate and colorectal cancer. This project is based on recent findings that selected covalent histone modifications and their modifying enzymes can be early markers of tumourigenesis. For this purpose, the following will be applied. a) selected covalent histone modification like acetylation, methylation, phosphorylation, ubiquitination among others b) their modifying enzymes, like DNA (de)methylases and histone (de)acetylases, (de)methyltransferases c) appropriate diagnostic methods and tests for detection of selected markers in clinical samples. These markers are revealed from studies in cell and animal models as well from patient cohorts. Non-invasive diagnostic methods based on technologies developed in the participating organizations will be tested in clinical samples. Appropriately selected clinical samples will be utilized according to EU and national ethical procedures. The major task of this consortium will be the development of methods to be applied in the clinic for the immediate benefit of cancer patients.