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Issue link: https://clinicalomics.epubxp.com/i/853204
www.clinicalomics.com July/August 2017 Clinical OMICs 21 d e m o n s t r a t - ing moderate success in this area, and what has in the past seemed an unachievable goal has moved slightly closer to reality. Cell-free DNA Revolution In the late 1990s, Dr. Lo and colleagues published research showing that cfDNA could be detected in maternal blood and that a significant proportion, made up of placental tro- phoblast cells, was from the fetus. The first maternal blood tests for fetal cfDNA on the mar- ket were for Down syndrome alone, but very quickly went on to cover Patau and Edwards syndromes and sex chromo- some aneuploidies. Six years down the line, tests for many additional abnormalities, including deletion syndromes such as DiGeorge, have been developed, but the accuracy at detecting these sub-chromosomal abnormalities remains suboptimal. "There are cfDNA-based diagnostic tests targeting known microdeletions but more data is needed to establish perfor- mance characteristics in large high-risk and low-risk popu- lations," commented molecular diagnostics expert Ahmad Abou Tayoun, Ph.D., from the University of Pennsylvania. Dr. Tayoun added: "Although fetal sequence variant detection can be, and has been, performed using cfDNA on a research basis, this is still not mature enough to be used routinely in the clinic. Such testing requires sophisticated yet highly reproduc- ible and robust bioinformatics pipelines (to detect the smaller proportion of fetal DNA [~10%] in mater- nal blood) that are still beyond the capabilities of most molecular diagnostic labs." When asked about performance of cfDNA tests for sub- chromosomal disorders, Dr. Lo said: "There is actually no consensus at the moment." But he added that "a num- ber of experts in the field are trying to improve the spec- ificity of the tests by looking at characteristics of the fetal DNA that can distinguish it from the maternal DNA in the mother 's blood." Dr. Lo's team has shown that fetal cfDNA is shorter than maternal cfDNA. They have also discovered that when the DNA breaks into fragments in plasma, there are some preferred ending sites that could be preferentially cleaved if the DNA is from the mother versus from the baby and vice versa. "A key factor that will enhance the use of cfDNA clini- (continued on next page) Li Ka Shing Institute of Health Sciences