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Cell-free DNA (cfDNA)

aka cfDNA, cell-free DNA, circulating cell-free DNA, plasma DNA, liquid biopsy, plasma NGS, plasma genotyping, blood-based genotyping, tissue-informed, tumour-informed, tumor-informed, tumour-naive, tumor-naive, fragmentomics

Short pieces of DNA floating in the blood, shed by dying cells all over the body. Most is from normal cells; the small tumour-derived fraction (ctDNA) is what liquid biopsies fish out.

A tube of blood contains nanograms of cell-free DNA, of which tumour DNA may be 0.01-10%. Assays detect it by deep sequencing with error correction (Guardant360, FoundationOne Liquid, MSK-ACCESS), by tumour-informed panels built from the patient's own tumour mutations (Signatera, RaDaR), or by methylation and fragment-size patterns that also reveal the tissue of origin (Galleri, fragmentomics). Uses span genotyping when tissue is scarce, resistance monitoring, MRD after surgery and multi-cancer screening. Pitfalls are CHIP-derived variants, low shedding by some tumours (brain, kidney) and pre-analytic handling, hence dedicated collection tubes.

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Pathology & biomarkers

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