{"entity":{"id":"paper-jamshidi-ccga1-cfdna-approaches-cancer-cell-2022","kind":"paper","name":"Evaluation of cell-free DNA approaches for multi-cancer early detection","aka":[],"tldr":"GRAIL compared ten ways of reading free-floating DNA in the same blood samples and found that methylation worked best both for spotting cancer and for saying where it was.","summary":"In the first substudy of the Circulating Cell-free Genome Atlas (NCT02889978), ten machine-learning classifiers built on different cell-free DNA features were trained on the same samples and independently validated. At 98% specificity, whole-genome methylation, single-nucleotide variants with white-blood-cell background removal, and combined scores gave the highest cancer signal sensitivity. The circulating tumour allele fraction predicted classifier performance better than clinical stage or tumour type, and whole-genome methylation best predicted cancer signal origin, which informed the targeted methylation test.","asOf":"2026-10-29","links":[{"label":"Cancer Cell 2022: CCGA first substudy","url":"https://doi.org/10.1016/j.ccell.2022.10.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36400018/"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced","cfdna-methylation-testing","fragmentomics"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":["ctdna","cfdna"],"trials":["ccga"],"people":["eric-klein"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2022,"doi":"10.1016/j.ccell.2022.10.022","pmid":"36400018","authors":"Jamshidi A, Liu MC, Klein EA, et al.","paperType":"observational","findings":["Whole-genome methylation among the most sensitive approaches at 98% specificity.","Tumour allele fraction in blood predicted detection better than stage.","Methylation best predicted cancer signal origin."],"whatItMeans":"Whether a cancer is found depends mostly on how much tumour DNA it sheds into the blood, which is why small early cancers are often missed by every approach.","caveats":["Case-control samples; comparisons are within one company's platform.","No absolute sensitivity figures in the abstract."],"changedPractice":false},"route":"/key-papers/paper-jamshidi-ccga1-cfdna-approaches-cancer-cell-2022/","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":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/"},{"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/"}],"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/"}],"trial":[{"id":"ccga","kind":"trial","name":"CCGA (Circulating Cell-free Genome Atlas)","route":"/trials/ccga/"}],"person":[{"id":"eric-klein","kind":"person","name":"Eric A. Klein","route":"/people/eric-klein/"}],"journal":[{"id":"cancer-cell","kind":"journal","name":"Cancer Cell","route":"/journals/cancer-cell/"}]}}