PhD R.G. (Ruben) Boers

Below is a brief summary of the dissertation:

Methylation of the DNA is crucial for cells to be able to turn genes off. During early development of an embryo, all cells get their specific DNA methylation patterns depending on which tissue they will form. Although DNA methylation patterns are very stable throughout life, in cancer the DNA methylation patterns are dramatically changed. In this thesis we developed a novel method (MeD-seq) that is able to detect all these DNA methylation changes at much lower costs on very small amounts of DNA compared to other methods. Therefore, MeD-seq can be used to detect and classify cancers by using DNA from blood plasma. This is further enhanced by the DNA methylation database we generated that includes all gynaecological cancers and associated healthy tissues. This database is still being expanded and serves as a basis for cancer detection and treatment monitoring. In addition, we developed a creative and novel tool, called DCM-Time machine (DCM-TM), which uses a form of DNA methylation normally only present in bacteria to label genes that are active. Using DCM-TM we are able to “look back in time” to see which genes were turned on in the past. Initially, MeD-seq was developed to be able to perform experiments using DCM-TM. However, since MeD-seq proved to be very useful for translational and clinical studies, it shows how fundamental research questions, like DCM-TM, pushes scientists to develop novel methods that can be applied to a much broader field than anticipated at first.