DNA can be damaged by a variety of mutagenic processes, like smoking and UV-radiation. Cells can repair the damage to their DNA, but when this does not happen or happens incorrectly, mutations can occur. Different combinations of mutagenic and DNA-repair processes can result in different mutation patterns. By investigating these patterns, we can attempt to determine the mutational processes that were active in a cell. During my PhD I investigated the mutations patterns of both healthy cells as well as childhood cancers to improve our understanding of the origin of cancer. First, I investigated the blood and intestinal stem cells of foetuses with and without Down syndrome. Foetal cells had a higher mutation rate than adults and this rate was even higher in foetuses with Down syndrome, which could contribute to their increased chance of developing cancer during their first years. After this I made the second version of MutationalPatterns, which is a software package to investigate mutational patterns. I then also applied this package on cell with a reduced DNA-repair capacity. Next, I investigated the mutation accumulation of mitochondria. I found that most mitochondrial mutations in cancer were the result of normal mutation accumulation. Finally, I worked on a pipeline to analyse the genomes of single cells, instead of groups of cells. I then applied this pipeline on both healthy blood cells as well as on the blood cells of a leukaemia patient.