# A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA

Source: https://onco.cc/key-papers/paper-doebley-griffin-nucleosome-profiling-nat-commun-2022/  
OnCo record `paper-doebley-griffin-nucleosome-profiling-nat-commun-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A method that reads whether a breast cancer still carries the oestrogen receptor from the DNA in a blood sample, when there is enough tumour DNA there.

## Summary

Griffin profiles nucleosome protection and accessibility from cell-free DNA at as low as 0.1x whole-genome coverage, with a GC correction tailored to fragment size. It predicted oestrogen receptor subtype in 139 patients with metastatic breast cancer with at least 5 per cent detectable ctDNA, with an area under the curve of 0.89, and 0.96 in independent cohorts.

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: Nature Communications
- Year: 2022
- DOI: 10.1038/s41467-022-35076-w
- Authors: Doebley AL, Ko M, Liao H, et al.
- Findings: ER subtype predicted with AUC 0.89 in 139 patients with at least 5% ctDNA.; AUC 0.96 in independent validation cohorts.
- What it means: The phenotype of advanced breast cancer, not only its mutations, can be read from blood. The method needs percent-level tumour DNA, so it does not yet reach residual disease after surgery.
- Caveats: Metastatic disease, tumour fraction at least 5%.; In the full text, performance was lower between 5 and 10 per cent tumour fraction than above it.

## Sources

- Doebley et al., Nat Commun 2022: https://doi.org/10.1038/s41467-022-35076-w
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36463275/

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [cfDNA fragmentomics](https://onco.cc/technologies/fragmentomics/), [Griffin (nucleosome profiling of cell-free DNA)](https://onco.cc/technologies/griffin-nucleosome-profiling/)
- targets: [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/)
- journals: [Nature Communications](https://onco.cc/journals/nature-communications/)
- ideas: [Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left](https://onco.cc/ideas/idea-same-fragment-methylation-and-mutation/)

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