{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:19Z","timestamp":1792790359165,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Bioinformatics","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01CA269805"],"award-info":[{"award-number":["R01CA269805"]}]},{"name":"NIH","award":["R01HG012573"],"award-info":[{"award-number":["R01HG012573"]}]},{"name":"NIH","award":["UM1DA058230"],"award-info":[{"award-number":["UM1DA058230"]}]},{"name":"CDMRP","award":["OC230088"],"award-info":[{"award-number":["OC230088"]}],"id":[{"id":"https:\/\/ror.org\/03g2zjp07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Copy-number amplifications drive cancer evolution through increased oncogene dosage. Mutations acquired before a gain are co-amplified, so their multiplicity places successive gains on a molecular timescale. This principle has been used to time individual gains and whole-genome duplication (WGD), but possible gain histories multiply rapidly with copy number, confining existing methods to low copy-number states or predefined scenarios and leaving oncogene-bearing amplifications unresolved. Here we describe a mathematical framework to systematically enumerate every allele-specific gain route to a copy-number state and derive an analytical timing for each gain, implemented in a method called Tau. Across pan-cancer genomes, punctuated multichromosomal events account for roughly three-quarters of clonal gains. Most are WGD, acquired early and often repeated within a doubling-prone subset, but a distinct, predominantly monoallelic class recurs on tumor-type-specific chromosomes, representing a coordinated mode separate from doubling. Strikingly, the highest copy-number states are reached not gradually but in abrupt bursts that cluster around WGD and contain more gains than doubling alone can produce, recurring at oncogenes. WGD is therefore not a passive doubling but a window in which localized oncogene amplification becomes far more frequent. By resolving the order of gains and the mutational processes shifting between them, Tau establishes punctuated amplification as a pervasive mode of cancer genome evolution.<\/jats:p>","DOI":"10.64898\/2026.09.23.753832","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:55:11Z","timestamp":1790708111000},"source":"Crossref","is-referenced-by-count":0,"title":["Complete timing of copy-number amplification histories reveals whole-genome duplication dynamics and coincident oncogene amplification bursts"],"prefix":"10.64898","author":[{"given":"Joseph","family":"Brew","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-960X","authenticated-orcid":false,"given":"Peter J.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Harvard 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