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Although being the standard in clinical oncology, analyzing mutations in tumor tissue comes with considerable drawbacks. Biopsies can significantly increase the costs of patient care, are inconvenient from a scheduling perspective and not without clinical complications (1). Moreover, they are subject to selection bias due to tumor heterogeneity, can be difficult to obtain in sufficient amounts and the information provided is restricted to a static time point (2-3).
It is now well established that cells shed small DNA fragments into the circulation with most of this DNA being compartmentalized in the plasma component of whole blood (4-12). The specific detection of tumor-derived cell-free DNA has been shown to correlate with tumor burden, to a change in response to treatment or surgery, and to indicate that subpopulations of tumor cells that are resistant to treatment can proliferate in response to therapy (13,14). Therefore circulating tumor DNA can serve as liquid biopsy that can be used for a variety of clinical and investigational applications without the need for physical biopsies.