Figure 6.

Origins of cell-free DNA. When a cell dies through either programmed cell death (apoptosis) or necrosis, its cellular contents (including DNA from the nucleus) are released into the bloodstream. At this point, the DNA becomes “cell-free DNA” and is rapidly degraded into small fragments through the action of circulating enzymes known as “DNAses.” As a result, most cfDNA fragments found in circulation are typically short, averaging 167 nucleotides in length in both humans and dogs (166, 167). While both healthy cells and tumor cells contain DNA that becomes cfDNA in circulation, only tumor cells will harbor somatic genomic alterations in cancer-related genes. Detection of such genomic alterations in the cfDNA of a patient is thus indicative of the presence of tumor cells in the body, providing the rationale for “liquid biopsy” testing approaches (Note: cfDNA exists as both single stranded DNA and double stranded DNA; only single stranded DNA is depicted here, for illustrative purposes).