PhD defence T. (Teoman) Deger

Below is a brief summary of the dissertation:

This thesis describes novel uses of liquid biopsies for cancer patients. Tumors release genomic material into the bloodstream. The presence of these bloodborne materials is in low abundance and thus must be enriched and/or isolated prior to molecular characterization.

One example of such bloodborne biomarkers is circulating tumor cells (CTCs). CTCs are cells which have detached from the tumor and are present in the bloodstream. As single CTCs contain a full tumor genome, these cells are coveted biomarkers. Studies have already shown that the number of CTCs is predictive of disease outcome. However, molecular analysis is not widely applied yet. This thesis describes the isolated of individual CTCs from a blood sample and describes how the DNA can be used for copy number profiling.

Another example of bloodborne biomarkers is circulating tumor DNA (ctDNA). Dying tumor cells release ctDNA into the bloodstream where it is a part of the total cell-free DNA (cfDNA). The total cfDNA can be isolated from a blood plasma, after which the ctDNA within can be detected. This thesis describes how chromosomal copy-number changes of cfDNA can be detected to indicate presence of ctDNA.

This thesis also describes how genome-wide methylation patterns can be detected in cfDNA. Detection of tumor-specific methylation patterns, as well as cell-type-specific methylationpatterns (which are generally not detected in healthy subjects), can be used as a sensitive monitoring tool.

Together, the techniques described in this thesis aim to potentiate minimal invasive detection of tumor biomarkers.