{"entity":{"id":"paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020","kind":"paper","name":"Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring","aka":[],"tldr":"Reading the whole genome of DNA in the blood, rather than a few genes very deeply, let researchers detect tumour DNA at one part in 100,000 by adding up thousands of mutations.","summary":"The authors found that low tumour fraction combined with the limited number of DNA fragments in a blood sample restricts low-burden monitoring by deep targeted sequencing, and reasoned that breadth could replace depth. Whole-genome sequencing of cell-free DNA, integrating the signal of thousands of somatic mutations found in solid tumours, reached tumour fraction detection sensitivity as low as 10⁻⁵. The approach tracked tumour burden over time and detected postoperative residual disease, which was associated with adverse outcome.","asOf":"2026-10-20","links":[{"label":"Zviran et al., Nat Med 2020","url":"https://doi.org/10.1038/s41591-020-0915-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32483360/"}],"tags":["precision"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["mrd-testing","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2020,"doi":"10.1038/s41591-020-0915-3","pmid":"32483360","authors":"Zviran A, Schulman RC, Shah M, et al.","paperType":"methods","findings":["Deep targeted sequencing is limited by the number of DNA fragments in the sample, not only by sequencing depth.","Whole-genome integration of thousands of mutations reached a tumour fraction detection sensitivity as low as 10⁻⁵."],"whatItMeans":"It explains why adding sequencing depth to a small panel stops helping, and points to whole-genome and multi-mutation tests as the way to see less tumour DNA.","caveats":["Proof of principle; clinical performance in prospective trials is a separate question."]},"route":"/key-papers/paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020/","neighbours":{"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"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/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}