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Characteristics, properties, and potential applications of circulating cell-free dna in clinical diagnostics: a focus

Karen Sherwood1, Eric T Weimer2

  • 1University of British Columbia, Department of Pathology & Laboratory Medicine, Vancouver, Canada.

Journal of Immunological Methods
|September 30, 2018
PubMed

Insights

Cell-free DNA (cfDNA) shows promise as a biomarker for detecting solid organ transplant rejection. Research indicates cfDNA levels correlate with biopsy results, suggesting its potential for noninvasive monitoring.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Cell-free DNA (cfDNA), fragments of DNA circulating in the bloodstream, were discovered in 1948.
  • Initially studied for various disease states, cfDNA analysis advanced with the Human Genome Project.
  • cfDNA is typically 150 bp double-stranded DNA, released during apoptosis and necrosis, found as monomers, dimers, and trimers.

Purpose of the Study:

  • To evaluate the role and clinical utility of cfDNA as a biomarker in disease states.
  • To explore the application of cfDNA analysis in solid organ transplantation, building on its success in noninvasive prenatal testing (NIPT).
  • To assess cfDNA as a surrogate marker for solid organ transplant rejection.

Main Methods:

  • Characterization of cfDNA in various patient populations and specimen types (serum, Streck, plasma).
  • Interrogation of tumor markers using cfDNA, particularly in cancer patients.
  • Analysis of cfDNA in studies examining solid organ transplantation.

Main Results:

  • Serum yields the highest cfDNA but has more genomic contamination than Streck or plasma specimens.
  • Noninvasive prenatal testing (NIPT) is the most successful clinical application of cfDNA, achieving high sensitivity and specificity for aneuploidy.
  • Studies in solid organ transplantation identified cfDNA as a surrogate marker for rejection, showing high concordance with biopsy results.

Conclusions:

  • cfDNA has emerged as a gold-standard biomarker for NIPT.
  • The application of cfDNA analysis to solid organ transplantation is a promising diagnostic target.
  • While promising, further prospective studies are needed to establish the clinical utility of cfDNA in monitoring solid organ transplant rejection.
Keywords:
BiomarkerCell-free DNAMolecular diagnosticsTransplantation

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