WGS_Liver_Cancer_Mouse_Project

This study seeks a basic understanding of the underlying principles of mutagenesis. Previous studies have revealed that mutations do not occur randomly in the genome. Studies searching for causality of these patterns found that regional chromatin organisation influences the mutation rates such that mutation rates are higher in repressed regions possibly due to late replication and lower in actively transcribed regions. However, these studies have overlaid chromatin profiles with cancer genomes from different cell types/sources and used long-term in vitro cultured cell lines. In our study, we use a chemically induced liver cancer model in mice (DEN-induced HCC) to link the epigenetic state of the target organ (liver) at the moment of carcinogen treatment with the emerging patterns of genetic changes in the resulting cancers. Thus we only interrogate the same cell type before and after carcinogen insult and at no point do we introduce possible cell culture artefacts. By using several mouse strains differing in their epigenetic profiles we can test if these principles are universal.