Abstract

Cancer Epigenetics: Shaping the Tumor Methylome

Frank Lyko, Group Leader, German Cancer Research Center

Aberrant DNA methylation patterns are one of the earliest and most consistent hallmarks of human cancer cells. However, the factors that shape the tumor methylome remain poorly understood. We are using various technologies to analyze DNA methylation and hydroxymethylation patterns on the genome scale. Prominent examples include the Illumina Infinium methylation array platform and next-generation sequencing-based approaches. Most of our activities focus on mouse models that are deficient for defined epigenetic factors. For example, we have shown that loss of Dnmt3a, a DNA methyltransferase that has been found to be mutated in several forms of cancer, causes hypomethylation and gene deregulation in large, active chromosome domains. We have also shown that combined deficiency for the DNA hydroxymethylases Tet1 and Tet2 results in substantially increased epigenetic plasticity with variably increased methylation levels. The similarities between these epigenetic alterations and the known features of the human cancer methylome are currently being investigated in detail. In addition, we are also analyzing the influence of contextual factors, such as aging and chronic inflammation and current resuslts from these studies will be presented.