# A computational framework for sensitive tumor detection and accurate subtyping using shallow cell-free DNA methylome sequencing

Source: https://onco.cc/key-papers/paper-paoli-meter-methylome-subtyping-genome-med-2026/  
OnCo record `paper-paoli-meter-methylome-subtyping-genome-med-2026` (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 DNA methylation in blood to measure metastatic breast cancer and call its oestrogen receptor status without tumour tissue.

## Summary

METER exploits tumour-type-specific DNA methylation patterns for ctDNA detection, quantification and subtyping from plasma low-pass (0.5 to 1x) whole-methylome sequencing. In longitudinal samples from metastatic breast cancer it showed a stronger association with clinical outcomes than other ctDNA methods and matched circulating tumour cell counts, even at tumour content below 3 per cent. In the full text, oestrogen receptor calls in samples with at least 5 per cent tumour content reached an accuracy of 0.93 (95% CI 0.85 to 0.97) when the MIMESIS-1 and MIMESIS-2 cohorts were combined.

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: Genome Medicine
- Year: 2026
- DOI: 10.1186/s13073-026-01603-3
- Authors: Paoli M, Galardi F, Nardone A, et al.
- Findings: Associated with outcome more strongly than other ctDNA methods and CTC counts, including below 3% tumour content.; ER status accuracy 0.93 at 5% tumour content or more (80 ER-positive, 12 ER-negative samples; full text).
- What it means: Methylation in blood can say whether advanced breast cancer still carries the oestrogen receptor. Subtyping still needs percent-level tumour content.
- Caveats: Few ER-negative samples.; Metastatic disease only.

## Sources

- Paoli et al., Genome Med 2026: https://doi.org/10.1186/s13073-026-01603-3
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41634848/

## 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: [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [METER (methylome-based ctDNA detection and subtyping)](https://onco.cc/technologies/meter-methylome-subtyping/)
- 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/)
- 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/)

---
JSON: https://onco.cc/api/v1/entities/paper-paoli-meter-methylome-subtyping-genome-med-2026.json