# Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer

Source: https://onco.cc/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/  
OnCo record `paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Comparing a blood test with a needle biopsy taken the same day showed that when the blood carried enough tumour DNA, it found everything the biopsy found.

## Summary

Targeted sequencing across 72 clinically relevant genes was performed on 45 plasma cell-free DNA samples collected at the time of a metastatic tissue biopsy in men with metastatic castration-resistant prostate cancer, and the alterations were compared with exome sequencing data from the matched tissue. Seventy-five point six per cent of the cell-free DNA samples had a circulating tumour DNA proportion greater than 2% of total cell-free DNA. In those men, all somatic mutations identified in the matched metastatic tissue biopsies were concurrently present in circulating tumour DNA, and the hierarchy of variant allele fractions for shared mutations was closely similar between the two. Copy-number profiles between matched liquid and solid biopsy were highly correlated and individual copy-number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplification in 22 samples, 64.7%, SPOP mutation in 3, 8.8%, and inactivating alterations in TP53, PTEN, RB1, APC, CDKN1B, BRCA2 and PIK3R1. In several men, circulating tumour DNA sequencing revealed changes not present in the paired solid biopsy, including alterations in the androgen receptor, WNT and PI3K pathways.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Journal of the National Cancer Institute
- Year: 2017
- DOI: 10.1093/jnci/djx118
- Authors: Wyatt AW, Annala M, Aggarwal R, et al.
- Findings: Circulating tumour DNA above 2% of total cell-free DNA in 75.6% of samples.; In those samples, every somatic mutation found in matched tissue was also found in plasma.; Copy-number calls in actionable genes 88.9% concordant.; Plasma revealed AR, WNT and PI3K pathway changes absent from the paired tissue in several men.
- What it means: It is the study that justified using plasma instead of a bone biopsy in this disease, with the honest caveat attached: the concordance holds only above a tumour fraction threshold, and below it the test is uninformative rather than negative.
- Caveats: Forty-five paired samples at academic centres.; Nearly a quarter of samples fell below the 2% tumour fraction threshold.; A 72-gene panel, so genes outside it were not compared.

## 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
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29206995/

## Connected records

- 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/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PTEN](https://onco.cc/targets/pten/), [RB1](https://onco.cc/targets/rb1/), [SPOP](https://onco.cc/targets/spop/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- 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/)
- journals: [JNCI: Journal of the National Cancer Institute](https://onco.cc/journals/jnci/)
- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/)

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