Figure 5: ctDNA formation. Most of ctDNAs are not derived from CTCs, they are released into bloodstream when tumor cells undergo apoptosis or necrosis processes instead. ctDNAs then circulate predominantly in the form of nucleosome to retain some features of nuclear chromatin [28-30]. In addition to genetic mutations, cancer-specific patterns of epigenetic modification, such as methylation, can be found in detached tumor cells in body fluids [32].