{"entity":{"id":"paper-paoli-meter-methylome-subtyping-genome-med-2026","kind":"paper","name":"A computational framework for sensitive tumor detection and accurate subtyping using shallow cell-free DNA methylome sequencing","aka":[],"tldr":"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.","asOf":"2026-11-04","links":[{"label":"Paoli et al., Genome Med 2026","url":"https://doi.org/10.1186/s13073-026-01603-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41634848/"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["diagnostics"],"technologies":["meter-methylome-subtyping","methylation-profiling"],"targets":["estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Genome Medicine","year":2026,"doi":"10.1186/s13073-026-01603-3","pmid":"41634848","authors":"Paoli M, Galardi F, Nardone A, et al.","paperType":"methods","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)."],"whatItMeans":"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."]},"route":"/key-papers/paper-paoli-meter-methylome-subtyping-genome-med-2026/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"meter-methylome-subtyping","kind":"technology","name":"METER (methylome-based ctDNA detection and subtyping)","route":"/technologies/meter-methylome-subtyping/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"term":[{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"idea":[{"id":"idea-same-fragment-methylation-and-mutation","kind":"idea","name":"Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left","route":"/ideas/idea-same-fragment-methylation-and-mutation/"}]}}