# Cell-free DNA (cfDNA)

Source: https://onco.cc/terms/cfdna/  
OnCo record `cfdna` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: 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; liquid biopsies

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cell-free_fetal_DNA
- Wikipedia: https://en.wikipedia.org/wiki/Cell-free_fetal_DNA

## Connected records

- terms: [CCGA: the Circulating Cell-free Genome Atlas behind the Galleri methylation test](https://onco.cc/terms/ccga-study/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Core needle biopsy and fine-needle aspiration (FNA)](https://onco.cc/terms/core-needle-biopsy/), [DETECT-A: a blood test plus PET-CT to screen 10,006 women with no symptoms](https://onco.cc/terms/detect-a-study/), [EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)](https://onco.cc/terms/egfr-mutation-subtypes/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [On-target resistance mutations (gatekeeper, solvent-front, compound)](https://onco.cc/terms/gatekeeper-mutation/), [Tumour markers (CEA, LDH, chromogranin, thyroglobulin)](https://onco.cc/terms/tumour-markers/), [Tumour-informed versus tumour-naive ctDNA assays](https://onco.cc/terms/tumour-informed-assay/)
- pathways: [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [cfDNA fragmentomics](https://onco.cc/technologies/fragmentomics/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- key papers: [Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors](https://onco.cc/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/), [Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer](https://onco.cc/key-papers/paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019/), [Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib](https://onco.cc/key-papers/paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018/), [Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference](https://onco.cc/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/), [Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab](https://onco.cc/key-papers/paper-gandara-blood-tmb-atezolizumab-nat-med-2018/), [Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer](https://onco.cc/key-papers/paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019/), [Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer](https://onco.cc/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/), [Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences](https://onco.cc/key-papers/paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022/), [Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)](https://onco.cc/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/), [Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer](https://onco.cc/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/), [Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients](https://onco.cc/key-papers/paper-sausen-ctdna-pancreatic-resection-nat-commun-2015/), [Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/), [Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set](https://onco.cc/key-papers/paper-klein-ccga3-mced-validation-ann-oncol-2021/), [Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers](https://onco.cc/key-papers/paper-cohen-ctdna-protein-liquid-biopsy-pancreatic-pnas-2017/), [Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer](https://onco.cc/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/), [DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms](https://onco.cc/key-papers/paper-detect-a-science-2020/), [Detecting neuroendocrine prostate cancer through tissue-informed cell-free DNA methylation analysis](https://onco.cc/key-papers/paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022/), [Detection and localization of surgically resectable cancers with a multi-analyte blood test](https://onco.cc/key-papers/paper-cohen-cancerseek-multi-analyte-blood-test-science-2018/), [Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer](https://onco.cc/key-papers/paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012/), [Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms](https://onco.cc/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/), [NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/), [Pancreatic cancer early detection biomarkers for high-risk individuals: insights from the PRECEDE consortium](https://onco.cc/key-papers/paper-worthington-precede-early-detection-biomarkers-ijc-2026/), [Plasma circulating tumor DNA in pancreatic cancer patients is a prognostic marker](https://onco.cc/key-papers/paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017/), [The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers](https://onco.cc/key-papers/paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/)
- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/)
- drugs: [SimpleScreen CRC](https://onco.cc/drugs/simplescreen-crc/)
- trials: [ECLIPSE (Shield blood test)](https://onco.cc/trials/eclipse-shield/), [PREEMPT CRC](https://onco.cc/trials/preempt-crc/)

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