{"entity":{"id":"paper-liu-ccga2-methylation-ann-oncol-2020","kind":"paper","name":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","aka":[],"tldr":"The study that chose methylation as the basis of the Galleri test: in 6,689 people it found cancers of more than 50 types with few false positives, though only about one in five stage I cancers.","summary":"A prospective case-control substudy of the Circulating Cell-free Genome Atlas (NCT02889978) and STRIVE (NCT03085888): 6,689 participants (2,482 with cancer of more than 50 types, 4,207 without) were divided into training and validation sets, and plasma cell-free DNA underwent bisulfite sequencing of a panel of more than 100,000 methylation regions. In validation, specificity was 99.3% (95% CI 98.3 to 99.8). Stage I to III sensitivity was 67.3% in 12 prespecified cancer types and 43.9% in all cancer types. Across all cancer types sensitivity was 18% at stage I, 43% at stage II, 81% at stage III and 93% at stage IV. Tissue of origin was predicted in 96% of samples with a cancer-like signal and was accurate in 93% of those.","asOf":"2026-10-29","links":[{"label":"Annals of Oncology 2020: CCGA second substudy","url":"https://doi.org/10.1016/j.annonc.2020.02.011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33506766/"},{"label":"ClinicalTrials.gov NCT02889978","url":"https://clinicaltrials.gov/study/NCT02889978"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced","cfdna-methylation-testing","methylation-profiling"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":[],"trials":["ccga","strive-grail"],"people":["eric-klein","charles-swanton"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2020.02.011","pmid":"33506766","authors":"Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV, CCGA Consortium","paperType":"observational","findings":["Specificity 99.3% in the validation set.","All cancer types: stage I 18%, stage II 43%, stage III 81%, stage IV 93% sensitivity.","Tissue of origin accurate in 93% of samples where it was predicted."],"whatItMeans":"Methylation patterns can flag many cancers and point to the organ, but the cancers most worth catching early were the ones least often found.","caveats":["Case-control design with cancers already diagnosed; screening performance is lower.","Sponsored by GRAIL."],"changedPractice":false,"participants":6689},"route":"/key-papers/paper-liu-ccga2-methylation-ann-oncol-2020/","neighbours":{"section":[{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"technology":[{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","route":"/technologies/cfdna-methylation-testing/"},{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/"}],"drug":[{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/"}],"company":[{"id":"grail","kind":"company","name":"GRAIL","route":"/companies/grail/"}],"trial":[{"id":"ccga","kind":"trial","name":"CCGA (Circulating Cell-free Genome Atlas)","route":"/trials/ccga/"},{"id":"strive-grail","kind":"trial","name":"STRIVE (GRAIL breast screening cohort)","route":"/trials/strive-grail/"}],"person":[{"id":"charles-swanton","kind":"person","name":"Charles Swanton","route":"/people/charles-swanton/"},{"id":"eric-klein","kind":"person","name":"Eric A. Klein","route":"/people/eric-klein/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}]}}