{"entity":{"id":"ctdna-tumour-fraction","kind":"biomarker","name":"Circulating tumour DNA fraction (and what a negative plasma result means)","aka":["ctDNA fraction","circulating tumour DNA fraction","tumour fraction","ctDNA%","cfDNA tumour content","plasma tumour fraction"],"tldr":"How much of the DNA floating in a blood sample came from the cancer. Above a few per cent, a plasma test finds what a biopsy would find; below it, a negative result means the test could not see, not that there is nothing there.","summary":"The number that decides whether a plasma genomic result can be believed. In 45 men with metastatic castration-resistant prostate cancer whose plasma was taken on the day of a metastatic tissue biopsy, 75.6% of samples had a circulating tumour DNA proportion above 2% of total cell-free DNA; in those samples, every somatic mutation found in the matched tissue was also present in plasma, the ranking of variant allele fractions was closely similar, and copy-number calls in actionable genes agreed 88.9% of the time (Wyatt 2017). At scale, 3,129 of 3,334 men with advanced prostate cancer, 94%, had detectable circulating tumour DNA at a median tumour fraction of 7.5%, and 67 of the 72 BRCA1 or BRCA2 mutations found in tissue were also found in plasma, 93%, including 100% of the variants predicted to be germline (Tukachinsky 2021). Two things confound the reading. Tumour fraction tracks disease burden, so plasma performs worst in the low-volume disease where an early answer would help most. And clonal haematopoiesis contributes variants that look somatic: at a 2% threshold, 13 of 69 men had such variants, and 7, 10%, had one in a gene used to decide PARP inhibitor candidacy, most often ATM, with clonal haematopoiesis accounting for almost half of all somatic repair-gene variants detected (Jensen 2021).","asOf":"2026-09-25","links":[{"label":"Wyatt et al., J Natl Cancer Inst 2017: concordance of circulating tumour DNA and matched metastatic tissue biopsy in 45 men with mCRPC","url":"https://doi.org/10.1093/jnci/djx118"},{"label":"Tukachinsky et al., Clin Cancer Res 2021: circulating tumour DNA profiling in 3,334 men with advanced prostate cancer, including 1,674 TRITON screening samples","url":"https://doi.org/10.1158/1078-0432.CCR-20-4805"},{"label":"Jensen et al., JAMA Oncol 2021: clonal haematopoiesis in DNA repair genes interfering with prostate cancer plasma cell-free DNA testing (69 men, paired whole-blood control)","url":"https://doi.org/10.1001/jamaoncol.2020.5161"}],"tags":["biomarker","prostate"],"related":["hrr-gene-mutation","ar-amplification","ctdna-mrd-positive"],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["brca","androgen-receptor","atm"],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution","homologous-recombination-repair","clonal-haematopoiesis"],"terms":["ctdna","cfdna","germline-vs-somatic","vus","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021","paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021","paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":[],"measurement":"ctdna-detection","scoringRule":{"text":"The estimated proportion of cell-free DNA in plasma that derives from tumour, reported with the genomic result; below the assay's tumour-fraction floor a negative result is uninformative rather than negative, and any repair-gene variant used for treatment selection should be checked against a paired whole-blood control.","quote":"Seventy-five point six percent of cfDNA samples had a ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic mutations identified in matched metastatic tissue biopsies were concurrently present in ctDNA.","source":"https://doi.org/10.1093/jnci/djx118","sourceLabel":"Wyatt et al., Journal of the National Cancer Institute 2017"},"thresholds":[],"definedBy":{"label":"Tukachinsky et al., Clin Cancer Res 2021: circulating tumour DNA profiling in 3,334 men with advanced prostate cancer","url":"https://doi.org/10.1158/1078-0432.CCR-20-4805"},"tests":[],"assays":[],"companionDiagnostics":[],"forPatient":"A blood test for cancer genes is easier than a bone biopsy and often gives the same answer. If it comes back with nothing found, that is not the same as nothing being there: it can mean the cancer was not shedding enough DNA into the blood that day, and a tissue sample may still be needed."},"route":"/biomarkers/ctdna-tumour-fraction/","neighbours":{"biomarker":[{"id":"ar-amplification","kind":"biomarker","name":"AR amplification (gene and upstream enhancer)","route":"/biomarkers/ar-amplification/"},{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"},{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"},{"id":"brca-somatic","kind":"biomarker","name":"Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations","route":"/biomarkers/brca-somatic/"}],"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"pathway":[{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"},{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"term":[{"id":"biopsy","kind":"term","name":"Biopsy","route":"/terms/biopsy/"},{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","route":"/terms/vus/"}],"paper":[{"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-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-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-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/"}]}}