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Summary PhD Defense Talk by Ariane Hallermayr

Liquid biopsy (LB) provides a promising biomarker for the non-invasive diagnosis of tumor patients. In particular, circulating tumor DNA (ctDNA), which closely correlates with the presence of tumor cells, has great potential for clinical application. A variety of different approaches have been described for the detection and quantification of ctDNA, ranging from targeted analysis of hotspot variants to whole genome sequencing (WGS). All of these approaches aim to detect either the presence or absence of ctDNA (minimal residual disease, MRD), or to detect the increase or decrease of ctDNA (therapy monitoring, TM). Within the scope of this PhD project, two independent methods for the highly sensitive and specific detection of ctDNA were developed and analytically and clinically validated: One targeted method, which is of interest in current clinical practice and one untargeted method, which allows the analysis of all tumor patients independent of their somatic mutational profile. Overall, the analytical and clinical validity of the targeted method for determining recurrence and progression in CRC was proven. In addition, a cost-effective and sensitive method for untargeted ctDNA analysis was developed and validated, extending the advantages of LB to all cancer patients.