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Single-cell copy-number profiling was used to analyze 62,646 aneuploid cells, in addition to bulk exome sequencing of most patients and single-nucleus RNA sequencing of six samples. In many cancer types, increased subclonal diversity was associated with higher CNA burden, whole-genome doubling (WGD), TP53 mutations, and increased geographic diversity. Cancer cells from each patient shared a set of truncal CNAs, suggesting evolution from a single ancestral cell. Many tumors accumulated CNAs in bursts of evolution, suggesting that punctuated evolution is common in diverse cancer types. This study greatly improves our knowledge of intratumoral chromosome diversity across human cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>This study presents one of the largest pan-cancer single-cell DNA sequencing analyses, profiling intratumoral copy-number heterogeneity across seven major cancer types. The data identified punctuated evolution, clonal origins, subclonal WGD, spatial heterogeneity, and associations between copy-number and transcriptional diversity, with implications for both cancer diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-25-0964","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T18:47:46Z","timestamp":1780944466000},"page":"2322-2343","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Pan-Cancer Single-Cell Analysis of Intratumoral Copy-Number Diversity and Evolution"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-7577","authenticated-orcid":false,"given":"Hanghui","family":"Ye","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Texas MD Anderson Cancer Center 1 Department of Systems Biology, , Houston, Texas."},{"name":"2Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center UTHealth Houston, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-0187","authenticated-orcid":false,"given":"Thomas O.","family":"McDonald","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jzgtq86","id-type":"ROR","asserted-by":"publisher"}],"name":"Dana-Farber Cancer Institute 3 Department of Data Science, , Boston, Massachusetts."},{"id":[{"id":"https:\/\/ror.org\/02jzgtq86","id-type":"ROR","asserted-by":"publisher"}],"name":"Dana-Farber Cancer Institute 4 Center for Cancer Evolution, , Boston, Massachusetts."},{"name":"5Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts."},{"name":"6Department of Biostatistics, Harvard T.H. 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