{"entity":{"id":"paper-hu-nat-genet","kind":"paper","name":"Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32424352 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n = 99) and treated (n = 100) metastases. Treated metastases often harbored private 'driver' mutations, whereas untreated metastases did not, suggesting that treatment promotes clonal evolution. Polyclonal seeding was common in untreated lymph node metastases (n = 17 out of 29, 59%) and distant metastases (n = 20 out of 70, 29%), but less frequent in treated distant metastases (n = 9 out of 94, 10%). The low number of metastasis-private clonal mutations is consistent with early metastatic seeding, which we estimated occurred 2-4 years before diagnosis across these cancers. Furthermore, these data suggest that the natural course of metastasis is selectively relaxed relative to early tumorigenesis and that metastasis-private mutations are not drivers of cancer spread but instead associated with drug resistance.\n\nIndexed on Europe PMC as PubMed record 32424352 (DOI 10.1038/s41588-020-0628-z). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2020","url":"https://doi.org/10.1038/s41588-020-0628-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32424352/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32424352"}],"tags":["europepmc-ingest"],"related":["metastasis-seeding-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-020-0628-z","pmid":"32424352","authors":"Hu Z, Li Z, Ma Z, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-hu-nat-genet/","neighbours":{"technology":[{"id":"metastasis-seeding-models","kind":"technology","name":"Metastatic seeding and dormancy models","route":"/technologies/metastasis-seeding-models/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}]}}