For example, the first and still the most widely deployed cfDNA assays are for non-invasive prenatal screening and assays to detect circulating microbial nucleic acids are commercially available. While cell-free DNA is often used synonymously with circulating tumor DNA, one should remember that circulating non-tumor and non-human nucleic acids may also be present in a sample. Nucleic acids may be shed into the blood by apoptotic and necrotic cells or by controlled secretion by living cells (Figure 2), usually with peaks in the range of 140-170 base pairs (bp), reflecting their association with nucleosomes 2, 3, 9. Since this original description, other research has found that increased cfDNA generally reflects a multitude of physiologic, such as pregnancy, and pathologic processes, including malignant and benign neoplastic conditions, inflammatory diseases, stroke, trauma, and sepsis 2,9. In 1977, scientists identified the presence of abnormally high levels of cell-free DNA (cfDNA) in the plasma and serum of cancer patients relative to healthy control patients and this cfDNA was presumed to represent mainly circulating tumor DNA (ctDNA) 1,5. The first description of circulating DNA free from cells in human blood was in 1948, but this garnered little attention in the broader scientific community 2.
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