The rapid development of DNA sequencing techniques has provided many important new insights into cancer biology, among them the identification of many somatic mutations in cancer tissues. Interestingly, many of the affected genes mediate epigenetic modifications either directly or indirectly, and the DNA methyltransferase Dnmt3a is a hotspots of somatic cancer mutations. Based on our 10 years research expertise in studying this enzyme, we plan in this project to analyse the effects of the cancer mutations in Dnmt3a. Our results will help to define the cancerogenic effect of somatic cancer Dnmt mutations and to understand how changes in DNA methylation lead to cancer. This will support the development of more targeted therapies for tumors containing mutated Dnmts. This project will be financed by the DFG in the Priority program 1463 “Epigenetic Regulation of normal hematopoiesis and its dysregulation in myeloid neoplasia”.