The Origin of Circulating Free DNA

Almost every report on circulating DNA identifies apoptosis or necrosis or both as the main source of free circulating DNA in serum and plasma. A hallmark of apoptosis is DNA degradation, in which chromosomal DNA is 1st cleaved into large fragments (50–300 kb) and subsequently into multiples of nucleosomal units (180–200 bp)(1). This ladder pattern is also visible after electrophoresis of circulating DNA and is frequently considered to be evidence that apoptosis may be the source of the observed DNA fragments in plasma(2)(3). It has been shown, however, that the characteristic ladder pattern can also be observed for actively released DNA(3). The contents of apoptotic cells are rapidly ingested by professional phagocytes or neighboring cells through mechanisms that are not fully understood(4), and the DNA is consequently completely digested by DNase II in lysosomes(1). Thus the possibility exists that DNA fragments released by …