Cell-free DNA (cfDNA) or circulating free DNA are degraded DNA fragments present in blood plasma and urine, that can be used to describe various forms of DNA freely circulating the bloodstream, that includes circulating tumour DNA (ctDNA), cell-free fetal DNA (cfDNA) and donor-derived cell-free DNA (ddcfDNA). These tests include screening to detect chromosomal abnormalities in the fetus and to identify post-transplantation rejection & specific mutations in cancer patients in gynecology, transplantation rejection, and oncology. ctDNA is a DNA present in the blood of the cancer patient due to the necrosis of a cancer cell. This free DNA can be utilized to detect cancer at a very early stage to bring down the mortality in cancer patients. It can detect specific mutations and helps in developing a personalized medicine and can also be used to monitor metastasis in real time, which may not be possible through traditional methods. ddcfDNA refers to the presence of cfDNA in the organ transplanted patient due to graft rejection. For instance, the rejection of the transplanted kidney is reported in about 4% of deceased-donor kidney transplant recipients within 1 year after transplant, and in 21% of cases, it is 5 years after transplantation. Cell-free DNA tests can detect graft rejection within few weeks of transplantation, which can help in bringing down the mortality rate to a significant extent.
According to a review article by Diana W. Bianchi, a senior researcher and institute director at the National Institutes of Health, “Sequencing the fetal DNA that circulates in a pregnant women’s blood holds promise for modern genomic medicine”. Fetal DNA sequencing improves the accuracy of prenatal screening tests for genetic conditions and since it is a non-invasive procedure they are preferred for prenatal screening. Traditional methods such as amniocentesis sometimes carry the risk of miscarriage. It is a simple blood test that analyzes fetal DNA that enters a pregnant woman’s blood from her placental cells and it most commonly is used to screen for fetal disorders such as Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau Syndrome). These tests can also be used to detect conditions resulting from an extra sex chromosome, from a missing part of a chromosome, and even for conditions resulting from a single gene mutation. According to the American College of Obstetricians and Gynecologists, the fetal DNA sequencing is a screening test and not a diagnostic test. Confirmatory testing using traditional methods should continue to be offered to women with positive results. These tests may reduce the need for risky traditional prenatal testing procedures among those women who test negative for any abnormalities.
However, there are few cases of false-positive results in cfDNA testing. Hence according to Dr. Currier, “cell-free DNA is a good second-tier screening test, but it does have false-positive and false-negative results, so pre-and post counselling addressing these limitations are essential”.