{"entity":{"id":"paper-razavi-cfdna-variant-sources-clonal-haematopoiesis-nat-med-2019","kind":"paper","name":"High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants","aka":[],"tldr":"Sequencing blood plasma and white blood cells side by side showed that most mutations found in plasma came from ageing blood-forming cells, not from the cancer.","summary":"A prospective study of 124 patients with metastatic cancer and contemporaneous tumour biopsies, and 47 controls without cancer, sequenced plasma cell-free DNA and matched white blood cell DNA across 508 genes and 2 megabases at more than 60,000-fold raw depth. The assay allowed de novo detection of tumour mutations and inference of tumour mutational burden, microsatellite instability and mutational signatures from plasma.\n\nThe vast majority of cell-free DNA mutations, 81.6 per cent in controls and 53.2 per cent in patients with cancer, had features consistent with clonal haematopoiesis. The authors concluded that clonal haematopoiesis is pervasive and that matched plasma and white blood cell sequencing is important for accurate interpretation.","asOf":"2026-10-20","links":[{"label":"Razavi et al., Nat Med 2019","url":"https://doi.org/10.1038/s41591-019-0652-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31768066/"}],"tags":["precision"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-haematopoiesis"],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2019,"doi":"10.1038/s41591-019-0652-7","pmid":"31768066","authors":"Razavi P, Li BT, Brown DN, et al.","paperType":"translational","findings":["53.2 per cent of cell-free DNA mutations in patients with cancer and 81.6 per cent in controls had features of clonal haematopoiesis.","Matched white blood cell sequencing separated blood-cell mutations from tumour mutations."],"whatItMeans":"A plasma test that does not also sequence the person's white blood cells can report a blood-cell mutation as a cancer mutation, and the commonest such genes include some that decide treatment.","caveats":["Research assay at more than 60,000-fold raw depth across 2 megabases.","The share was 81.6 per cent in people without cancer and 53.2 per cent in people with metastatic cancer, so it depends on how much tumour DNA is present."],"participants":171},"route":"/key-papers/paper-razavi-cfdna-variant-sources-clonal-haematopoiesis-nat-med-2019/","neighbours":{"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"}],"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/"}]}}