{"entity":{"id":"cfdna","kind":"term","name":"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","liquid biopsies"],"tldr":"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.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell-free_fetal_DNA","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell-free_fetal_DNA"}],"tags":[],"related":["ctdna","mrd","clonal-haematopoiesis","core-needle-biopsy"],"cancers":[],"sections":["diagnostics"],"technologies":["liquid-biopsy","mced","fragmentomics","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/cfdna/","neighbours":{"term":[{"id":"ccga-study","kind":"term","name":"CCGA: the Circulating Cell-free Genome Atlas behind the Galleri methylation test","route":"/terms/ccga-study/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"core-needle-biopsy","kind":"term","name":"Core needle biopsy and fine-needle aspiration (FNA)","route":"/terms/core-needle-biopsy/"},{"id":"detect-a-study","kind":"term","name":"DETECT-A: a blood test plus PET-CT to screen 10,006 women with no symptoms","route":"/terms/detect-a-study/"},{"id":"egfr-mutation-subtypes","kind":"term","name":"EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)","route":"/terms/egfr-mutation-subtypes/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"},{"id":"tumour-markers","kind":"term","name":"Tumour markers (CEA, LDH, chromogranin, thyroglobulin)","route":"/terms/tumour-markers/"},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","route":"/terms/tumour-informed-assay/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"paper":[{"id":"paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017","kind":"paper","name":"Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors","route":"/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/"},{"id":"paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019","kind":"paper","name":"Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer","route":"/key-papers/paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019/"},{"id":"paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","kind":"paper","name":"Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib","route":"/key-papers/paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018/"},{"id":"paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021","kind":"paper","name":"Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference","route":"/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/"},{"id":"paper-gandara-blood-tmb-atezolizumab-nat-med-2018","kind":"paper","name":"Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab","route":"/key-papers/paper-gandara-blood-tmb-atezolizumab-nat-med-2018/"},{"id":"paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019","kind":"paper","name":"Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer","route":"/key-papers/paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019/"},{"id":"paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","kind":"paper","name":"Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer","route":"/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/"},{"id":"paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022","kind":"paper","name":"Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences","route":"/key-papers/paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022/"},{"id":"paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","kind":"paper","name":"Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)","route":"/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/"},{"id":"paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018","kind":"paper","name":"Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer","route":"/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/"},{"id":"paper-sausen-ctdna-pancreatic-resection-nat-commun-2015","kind":"paper","name":"Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients","route":"/key-papers/paper-sausen-ctdna-pancreatic-resection-nat-commun-2015/"},{"id":"paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","kind":"paper","name":"Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer","route":"/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/"},{"id":"paper-klein-ccga3-mced-validation-ann-oncol-2021","kind":"paper","name":"Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set","route":"/key-papers/paper-klein-ccga3-mced-validation-ann-oncol-2021/"},{"id":"paper-cohen-ctdna-protein-liquid-biopsy-pancreatic-pnas-2017","kind":"paper","name":"Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers","route":"/key-papers/paper-cohen-ctdna-protein-liquid-biopsy-pancreatic-pnas-2017/"},{"id":"paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","kind":"paper","name":"Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer","route":"/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/"},{"id":"paper-detect-a-science-2020","kind":"paper","name":"DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms","route":"/key-papers/paper-detect-a-science-2020/"},{"id":"paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022","kind":"paper","name":"Detecting neuroendocrine prostate cancer through tissue-informed cell-free DNA methylation analysis","route":"/key-papers/paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022/"},{"id":"paper-cohen-cancerseek-multi-analyte-blood-test-science-2018","kind":"paper","name":"Detection and localization of surgically resectable cancers with a multi-analyte blood test","route":"/key-papers/paper-cohen-cancerseek-multi-analyte-blood-test-science-2018/"},{"id":"paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012","kind":"paper","name":"Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer","route":"/key-papers/paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012/"},{"id":"paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021","kind":"paper","name":"Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms","route":"/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/"},{"id":"paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","kind":"paper","name":"NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer","route":"/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/"},{"id":"paper-worthington-precede-early-detection-biomarkers-ijc-2026","kind":"paper","name":"Pancreatic cancer early detection biomarkers for high-risk individuals: insights from the PRECEDE consortium","route":"/key-papers/paper-worthington-precede-early-detection-biomarkers-ijc-2026/"},{"id":"paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017","kind":"paper","name":"Plasma circulating tumor DNA in pancreatic cancer patients is a prognostic marker","route":"/key-papers/paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017/"},{"id":"paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012","kind":"paper","name":"The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers","route":"/key-papers/paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012/"},{"id":"paper-lindeman-lung-molecular-testing-guideline-jto-2018","kind":"paper","name":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","route":"/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/"}],"biomarker":[{"id":"ctdna-tumour-fraction","kind":"biomarker","name":"Circulating tumour DNA fraction (and what a negative plasma result means)","route":"/biomarkers/ctdna-tumour-fraction/"},{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"}],"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"}],"drug":[{"id":"simplescreen-crc","kind":"drug","name":"SimpleScreen CRC","route":"/drugs/simplescreen-crc/"}],"trial":[{"id":"eclipse-shield","kind":"trial","name":"ECLIPSE (Shield blood test)","route":"/trials/eclipse-shield/"},{"id":"preempt-crc","kind":"trial","name":"PREEMPT CRC","route":"/trials/preempt-crc/"}]}}