Introduction to cell-free DNA
What is cell-free DNA?
cfDNA is DNA that typically circulates in fragments ranging from 120–220 base pairs, with a predominant fragment size of 170 base pairs. This corresponds to the length of DNA that can wrap around a nucleosome (147 bp), plus an additional stretch of DNA that links two nucleosome cores. The half-life of cfDNA in blood ranges from 15 minutes to 2.5 hours, and when it originates from tumor cells, it is referred to as circulating tumor DNA (ctDNA).
cfDNA in cancer research
In cancer research, cfDNA can provide biomarkers that can be used to gain molecular insights into the complexity of disease and help future development of diagnostics, treatments and monitoring of responses.
Cell-free DNA as a biomarker
Cell-free DNA (cfDNA) shed into the bloodstream or body fluids of healthy or disease-affected individuals is an important analyte in liquid biopsy. These circulating DNA fragments can reveal various alterations such as single nucleotide variants, insertions and deletions and larger chromosomal abnormalities, including copy translocations. Additional information, including structural variants or modifications, such as DNA methylation, would complete cfDNA assessment. All of these have potential use as cfDNA biomarkers (cell-free DNA biomarkers).
cfDNA holds great promise to improve clinical practice in several ways:
- By advancing basic disease research and improving our understanding of cfDNA release mechanisms and tissues of origin
- As a companion diagnostic for identifying cancer treatment options through analysis of a defined set of mutations or chromosomal aberrations
- For early disease detection in cancer, the identification of the tissue of origin, therapy monitoring and the assessment of emerging resistance or minimal residual disease monitoring
- For non-invasive prenatal testing (NIPT), enabling the detection of fetal chromosomal abnormalities by analyzing fetal DNA in maternal blood
- As a surrogate marker for post-transplant monitoring
These pages present our best practice recommendations and advice to support the standardization of methods for preanalytical cfDNA sample collection and preparation.