# Circulating tumour DNA fraction (and what a negative plasma result means)

Source: https://onco.cc/biomarkers/ctdna-tumour-fraction/  
OnCo record `ctdna-tumour-fraction` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

## Fields

- Kind: Biomarker
- Last checked: 2026-09-25
- Also known as: ctDNA fraction; circulating tumour DNA fraction; tumour fraction; ctDNA%; cfDNA tumour content; plasma tumour fraction
- Tags: biomarker; prostate

## Sources

- Wyatt et al., J Natl Cancer Inst 2017: concordance of circulating tumour DNA and matched metastatic tissue biopsy in 45 men with mCRPC: https://doi.org/10.1093/jnci/djx118
- 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: https://doi.org/10.1158/1078-0432.CCR-20-4805
- 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): https://doi.org/10.1001/jamaoncol.2020.5161

## Connected records

- biomarkers: [AR amplification (gene and upstream enhancer)](https://onco.cc/biomarkers/ar-amplification/), [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/), [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/), [Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations](https://onco.cc/biomarkers/brca-somatic/)
- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- pathways: [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/)
- terms: [Biopsy](https://onco.cc/terms/biopsy/), [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Variant of uncertain significance (VUS)](https://onco.cc/terms/vus/)
- key papers: [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/), [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/), [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/), [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/)

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