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Review

Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms

1
Institute of Computational Biotechnology, Graz University of Technology, Petersgasse 14(V), 8010 Graz, Austria
2
Institute for Laboratory Medicine, German Heart Centre, Technical University Munich, Lazarettstraße 36, 80636 Munich, Germany
3
CNA Diagnostics GmbH, Parkring 18, 8074 Grambach, Austria
4
BioTechMed Graz, Mozartgasse 12/II, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(21), 8062; https://doi.org/10.3390/ijms21218062
Received: 16 October 2020 / Revised: 27 October 2020 / Accepted: 27 October 2020 / Published: 29 October 2020
Through various pathways of cell death, degradation, and regulated extrusion, partial or complete genomes of various origins (e.g., host cells, fetal cells, and infiltrating viruses and microbes) are continuously shed into human body fluids in the form of segmented cell-free DNA (cfDNA) molecules. While the genetic complexity of total cfDNA is vast, the development of progressively efficient extraction, high-throughput sequencing, characterization via bioinformatics procedures, and detection have resulted in increasingly accurate partitioning and profiling of cfDNA subtypes. Not surprisingly, cfDNA analysis is emerging as a powerful clinical tool in many branches of medicine. In addition, the low invasiveness of longitudinal cfDNA sampling provides unprecedented access to study temporal genomic changes in a variety of contexts. However, the genetic diversity of cfDNA is also a great source of ambiguity and poses significant experimental and analytical challenges. For example, the cfDNA population in the bloodstream is heterogeneous and also fluctuates dynamically, differs between individuals, and exhibits numerous overlapping features despite often originating from different sources and processes. Therefore, a deeper understanding of the determining variables that impact the properties of cfDNA is crucial, however, thus far, is largely lacking. In this work we review recent and historical research on active vs. passive release mechanisms and estimate the significance and extent of their contribution to the composition of cfDNA. View Full-Text
Keywords: cell-free DNA; circulating DNA; liquid biopsy; circulating tumor DNA; active release of cfDNA; passive release of cfDNA; origins of cfDNA cell-free DNA; circulating DNA; liquid biopsy; circulating tumor DNA; active release of cfDNA; passive release of cfDNA; origins of cfDNA
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MDPI and ACS Style

Grabuschnig, S.; Bronkhorst, A.J.; Holdenrieder, S.; Rosales Rodriguez, I.; Schliep, K.P.; Schwendenwein, D.; Ungerer, V.; Sensen, C.W. Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms. Int. J. Mol. Sci. 2020, 21, 8062. https://doi.org/10.3390/ijms21218062

AMA Style

Grabuschnig S, Bronkhorst AJ, Holdenrieder S, Rosales Rodriguez I, Schliep KP, Schwendenwein D, Ungerer V, Sensen CW. Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms. International Journal of Molecular Sciences. 2020; 21(21):8062. https://doi.org/10.3390/ijms21218062

Chicago/Turabian Style

Grabuschnig, Stefan, Abel J. Bronkhorst, Stefan Holdenrieder, Ingund Rosales Rodriguez, Klaus P. Schliep, Daniel Schwendenwein, Vida Ungerer, and Christoph W. Sensen 2020. "Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms" International Journal of Molecular Sciences 21, no. 21: 8062. https://doi.org/10.3390/ijms21218062

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