{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:01:48Z","timestamp":1793152908076,"version":"4.5.0"},"reference-count":50,"publisher":"American Association for Cancer Research (AACR)","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A22745"],"award-info":[{"award-number":["A22745"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A22909"],"award-info":[{"award-number":["A22909"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A19771"],"award-info":[{"award-number":["A19771"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202778\/Z\/16\/Z"],"award-info":[{"award-number":["202778\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202778\/B\/16\/Z, 105104\/Z\/14\/Z"],"award-info":[{"award-number":["202778\/B\/16\/Z, 105104\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206314\/Z\/17\/Z"],"award-info":[{"award-number":["206314\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A26815"],"award-info":[{"award-number":["A26815"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA217376"],"award-info":[{"award-number":["CA217376"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA217376"],"award-info":[{"award-number":["CA217376"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA217376"],"award-info":[{"award-number":["CA217376"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Aneuploidy is near-ubiquitous in cancer and contributes to tumor biology. However, the temporal evolutionary dynamics that select for aneuploidy remain uncharacterized. We performed longitudinal genomic analysis of 755 samples from 167 patients with colorectal-derived neoplasias from different stages through metastasis and treatment. Adenomas had few copy number alterations (CNA) and most were subclonal, whereas cancers had many clonal CNAs, suggesting that progression goes through a CNA bottleneck. Individual colorectal cancer glands from the same tumor had similar karyotypes, despite evidence of ongoing instability at the cell level. CNAs in metastatic lesions, after therapy, and in late recurrences were similar to the primary. Mathematical modeling indicated that these data are consistent with the action of negative selection on CNAs that \u201ctrap\u201d cancer genomes on a fitness peak characterized by specific CNAs. Hence, progression to colorectal cancer requires traversing a rugged fitness landscape, whereas subsequent CNA evolution is constrained by negative selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>We profiled 167 long-term responders longitudinally (755 samples), documenting long-term cancer evolution. We found that a genetic bottleneck is required for progression and is associated with dramatic increase in CNAs but decrease in clonal diversity. After initiation, copy number evolution is constrained by negative selection through metastasis and treatment.<\/jats:p>\n                    <jats:p>See related commentary by Okada et al., p. 192<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-0813","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T14:50:20Z","timestamp":1769007020000},"page":"218-234","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Negative Selection Maintains Grossly Altered but Broadly Stable Karyotypes in Metastatic Colorectal Cancer"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-8777","authenticated-orcid":false,"given":"William C.H.","family":"Cross","sequence":"first","affiliation":[{"name":"1Rare Diseases and Cancer Evolution Lab, Centre for Cancer Research, School of Biological Sciences, University of Reading, Reading, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-3778","authenticated-orcid":false,"given":"Salpie","family":"Nowinski","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-068X","authenticated-orcid":false,"given":"George D.","family":"Cresswell","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."},{"name":"4St. Anna Children\u2019s Cancer Research Institute (CCRI), Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-3803","authenticated-orcid":false,"given":"Maximilian","family":"Mossner","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-4470","authenticated-orcid":false,"given":"Abhirup","family":"Banerjee","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0606-5150","authenticated-orcid":false,"given":"Bingxin","family":"Lu","sequence":"additional","affiliation":[{"name":"5Department of Cell and Developmental Biology, University College London, London, United Kingdom."},{"name":"6UCL Genetics Institute, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-4174","authenticated-orcid":false,"given":"Marc J.","family":"Williams","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"7Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3114-8772","authenticated-orcid":false,"given":"Georgios","family":"Vlachogiannis","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-8677","authenticated-orcid":false,"given":"Laura J.","family":"Gay","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-9137","authenticated-orcid":false,"given":"Ann-Marie","family":"Baker","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-4434","authenticated-orcid":false,"given":"Christopher","family":"Kimberley","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4090-7136","authenticated-orcid":false,"given":"Frederick J.H.","family":"Whiting","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-4932","authenticated-orcid":false,"given":"Hayley L.","family":"Belnoue-Davis","sequence":"additional","affiliation":[{"name":"8Department of Surgery and Cancer, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-4413","authenticated-orcid":false,"given":"Pierre","family":"Martinez","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"9Univ Lyon, Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre L\u00e9on B\u00e9rard, Cancer Research Center of Lyon, Lyon, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2803-9015","authenticated-orcid":false,"given":"Maria","family":"Traki","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6396-7298","authenticated-orcid":false,"given":"Viola","family":"Walther","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8661-7401","authenticated-orcid":false,"given":"Kane","family":"Smith","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-4131","authenticated-orcid":false,"given":"Javier","family":"Fernandez-Mateos","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7557-9128","authenticated-orcid":false,"given":"Erika","family":"Yara-Romero","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1624-4021","authenticated-orcid":false,"given":"Erica A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0156-3636","authenticated-orcid":false,"given":"Salvatore","family":"Milite","sequence":"additional","affiliation":[{"name":"10Computational Biology Research Centre, Human Technopole, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-3265","authenticated-orcid":false,"given":"Giulio","family":"Caravagna","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3996-0909","authenticated-orcid":false,"given":"Chela T.","family":"James","sequence":"additional","affiliation":[{"name":"10Computational Biology Research Centre, Human Technopole, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Elia","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-0275","authenticated-orcid":false,"given":"Alison","family":"Berner","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"11UCL Cancer Institute, UCL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8346-450X","authenticated-orcid":false,"given":"Chang-Ho","family":"Ryan Choi","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"12St. Mark\u2019s Hospital, London, United Kingdom."},{"name":"13St. George Hospital, Sydney, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-5916","authenticated-orcid":false,"given":"Pradeep","family":"Ramagiri","sequence":"additional","affiliation":[{"name":"14Tumour Profiling Unit (TPU), Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-9343","authenticated-orcid":false,"given":"Ritika","family":"Chauhan","sequence":"additional","affiliation":[{"name":"14Tumour Profiling Unit (TPU), Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-1131","authenticated-orcid":false,"given":"Nik","family":"Matthews","sequence":"additional","affiliation":[{"name":"14Tumour Profiling Unit (TPU), Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0519-9031","authenticated-orcid":false,"given":"Jamie","family":"Murphy","sequence":"additional","affiliation":[{"name":"8Department of Surgery and Cancer, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8252-7493","authenticated-orcid":false,"given":"Anthony","family":"Antoniou","sequence":"additional","affiliation":[{"name":"12St. Mark\u2019s Hospital, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6929-8082","authenticated-orcid":false,"given":"Susan K.","family":"Clark","sequence":"additional","affiliation":[{"name":"8Department of Surgery and Cancer, Imperial College London, London, United Kingdom."},{"name":"12St. Mark\u2019s Hospital, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2520-2744","authenticated-orcid":false,"given":"Miriam","family":"Mitchison","sequence":"additional","affiliation":[{"name":"15UCL Hospitals NHS Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-4250","authenticated-orcid":false,"given":"Jo-Anne","family":"Chin Aleong","sequence":"additional","affiliation":[{"name":"16Barts Health NHS Trust, The Royal London Hospital, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4390-8767","authenticated-orcid":false,"given":"Enric","family":"Domingo","sequence":"additional","affiliation":[{"name":"17Department of Oncology, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-8972","authenticated-orcid":false,"given":"Inmaculada","family":"Spiteri","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2386-4915","authenticated-orcid":false,"given":"Stuart A.C.","family":"McDonald","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4567-1639","authenticated-orcid":false,"given":"Darryl","family":"Shibata","sequence":"additional","affiliation":[{"name":"18Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3466-3569","authenticated-orcid":false,"given":"Miangela M.","family":"Lacl\u00e9","sequence":"additional","affiliation":[{"name":"19Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7113-4215","authenticated-orcid":false,"given":"Lai Mun","family":"Wang","sequence":"additional","affiliation":[{"name":"20Wellcome Trust Centre Human Genetics, University of Oxford, Oxford, United Kingdom."},{"name":"21Ludwig Institute, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0262-2674","authenticated-orcid":false,"given":"Morgan","family":"Moorghen","sequence":"additional","affiliation":[{"name":"12St. Mark\u2019s Hospital, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P.M.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"22Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-9134","authenticated-orcid":false,"given":"Marco","family":"Novelli","sequence":"additional","affiliation":[{"name":"11UCL Cancer Institute, UCL, London, United Kingdom."},{"name":"15UCL Hospitals NHS Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-564X","authenticated-orcid":false,"given":"Marnix","family":"Jansen","sequence":"additional","affiliation":[{"name":"11UCL Cancer Institute, UCL, London, United Kingdom."},{"name":"15UCL Hospitals NHS Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8233-0459","authenticated-orcid":false,"given":"Alan","family":"Watson","sequence":"additional","affiliation":[{"name":"23Department of Gastroenterology, Barts Health, Whipps Cross Hospital, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-5683","authenticated-orcid":false,"given":"Nicola","family":"Valeri","sequence":"additional","affiliation":[{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-3457","authenticated-orcid":false,"given":"Nicholas A.","family":"Wright","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9186-1604","authenticated-orcid":false,"given":"John A.","family":"Bridgewater","sequence":"additional","affiliation":[{"name":"11UCL Cancer Institute, UCL, London, United Kingdom."},{"name":"15UCL Hospitals NHS Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5007-1761","authenticated-orcid":false,"given":"Manuel","family":"Rodriguez-Justo","sequence":"additional","affiliation":[{"name":"11UCL Cancer Institute, UCL, London, United Kingdom."},{"name":"15UCL Hospitals NHS Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9459-1395","authenticated-orcid":false,"given":"Chris P.","family":"Barnes","sequence":"additional","affiliation":[{"name":"5Department of Cell and Developmental Biology, University College London, London, United Kingdom."},{"name":"6UCL Genetics Institute, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6771-1905","authenticated-orcid":false,"given":"Hemant M.","family":"Kocher","sequence":"additional","affiliation":[{"name":"16Barts Health NHS Trust, The Royal London Hospital, London, United Kingdom."},{"name":"24Centre for Tumour Biology, Barts Cancer Institute, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1476-6982","authenticated-orcid":false,"given":"Simon J.","family":"Leedham","sequence":"additional","affiliation":[{"name":"20Wellcome Trust Centre Human Genetics, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6709-9533","authenticated-orcid":false,"given":"Andrea","family":"Sottoriva","sequence":"additional","affiliation":[{"name":"10Computational Biology Research Centre, Human Technopole, Milan, Italy."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9582-1597","authenticated-orcid":false,"given":"Trevor A.","family":"Graham","sequence":"additional","affiliation":[{"name":"2Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"3Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"2026020910300722300_bib1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic and functional approaches to understanding cancer aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"2026020910300722300_bib2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrclinonc.2017.198","article-title":"Determinants and clinical implications of chromosomal instability in cancer","volume":"15","author":"Sansregret","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"2026020910300722300_bib3","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive molecular characterization of human colon and rectal cancer","volume":"487","author":"Cancer Genome Atlas Network","year":"2012","journal-title":"Nature"},{"key":"2026020910300722300_bib4","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41586-020-2698-6","article-title":"Pervasive chromosomal instability and karyotype order in tumour evolution","volume":"587","author":"Watkins","year":"2020","journal-title":"Nature"},{"key":"2026020910300722300_bib5","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1186\/gb-2011-12-4-r41","article-title":"GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers","volume":"12","author":"Mermel","year":"2011","journal-title":"Genome Biol"},{"key":"2026020910300722300_bib6","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1158\/1940-6207.CAPR-15-0130","article-title":"Assessment of esophageal adenocarcinoma risk using somatic chromosome alterations in longitudinal samples in Barrett\u2019s esophagus","volume":"8","author":"Li","year":"2015","journal-title":"Cancer Prev Res (Phila)"},{"key":"2026020910300722300_bib7","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/0016-5085(92)91185-7","article-title":"DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis","volume":"103","author":"Rubin","year":"1992","journal-title":"Gastroenterology"},{"key":"2026020910300722300_bib8","doi-asserted-by":"crossref","first-page":"e39217","DOI":"10.7554\/eLife.39217","article-title":"Systematic identification of mutations and copy number alterations associated with cancer patient prognosis","volume":"7","author":"Smith","year":"2018","journal-title":"Elife"},{"key":"2026020910300722300_bib9","doi-asserted-by":"crossref","first-page":"e37294","DOI":"10.7554\/eLife.37294","article-title":"Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death","volume":"7","author":"Hieronymus","year":"2018","journal-title":"Elife"},{"key":"2026020910300722300_bib10","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nm.3984","article-title":"Pan-cancer analysis of the extent and consequences of intratumor heterogeneity","volume":"22","author":"Andor","year":"2016","journal-title":"Nat Med"},{"key":"2026020910300722300_bib11","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1056\/NEJMoa1616288","article-title":"Tracking the evolution of non-small-cell lung cancer","volume":"376","author":"Jamal-Hanjani","year":"2017","journal-title":"N Engl J Med"},{"key":"2026020910300722300_bib12","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s43018-024-00787-0","article-title":"Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer","volume":"5","author":"Fernandez-Mateos","year":"2024","journal-title":"Nat Cancer"},{"key":"2026020910300722300_bib13","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.tig.2011.07.003","article-title":"The aneuploidy paradox: costs and benefits of an incorrect karyotype","volume":"27","author":"Sheltzer","year":"2011","journal-title":"Trends Genet"},{"key":"2026020910300722300_bib14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13059-024-03225-7","article-title":"Machine-learning analysis reveals an important role for negative selection in shaping cancer aneuploidy landscapes","volume":"25","author":"Jubran","year":"2024","journal-title":"Genome Biol"},{"key":"2026020910300722300_bib15","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41586-023-06266-3","article-title":"Cancer aneuploidies are shaped primarily by effects on tumour fitness","volume":"619","author":"Shih","year":"2023","journal-title":"Nature"},{"key":"2026020910300722300_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cancergencyto.2008.08.016","article-title":"Cancer-causing karyotypes: chromosomal equilibria between destabilizing aneuploidy and stabilizing selection for oncogenic function","volume":"188","author":"Li","year":"2009","journal-title":"Cancer Genet Cytogenet"},{"key":"2026020910300722300_bib17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41588-020-0584-7","article-title":"Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution","volume":"52","author":"L\u00f3pez","year":"2020","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib18","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/217624a0","article-title":"Evolutionary rate at the molecular level","volume":"217","author":"Kimura","year":"1968","journal-title":"Nature"},{"key":"2026020910300722300_bib19","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1158\/0008-5472.CAN-10-3667","article-title":"Paradoxical relationship between chromosomal instability and survival outcome in cancer","volume":"71","author":"Birkbak","year":"2011","journal-title":"Cancer Res"},{"key":"2026020910300722300_bib20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrg.2016.170","article-title":"The evolution of tumour phylogenetics: principles and practice","volume":"18","author":"Schwartz","year":"2017","journal-title":"Nat Rev Genet"},{"key":"2026020910300722300_bib21","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1038\/s41559-018-0642-z","article-title":"The evolutionary landscape of colorectal tumorigenesis","volume":"2","author":"Cross","year":"2018","journal-title":"Nat Ecol Evol"},{"key":"2026020910300722300_bib22","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/ng1768","article-title":"Genetic clonal diversity predicts progression to esophageal adenocarcinoma","volume":"38","author":"Maley","year":"2006","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/ng.3214","article-title":"A Big Bang model of human colorectal tumor growth","volume":"47","author":"Sottoriva","year":"2015","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib24","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41588-018-0128-6","article-title":"Quantification of subclonal selection in cancer from bulk sequencing data","volume":"50","author":"Williams","year":"2018","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib25","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/386623a0","article-title":"Genetic instability in colorectal cancers","volume":"386","author":"Lengauer","year":"1997","journal-title":"Nature"},{"key":"2026020910300722300_bib26","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1073\/pnas.0810276106","article-title":"Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancers","volume":"106","author":"Siegmund","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026020910300722300_bib27","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/s41588-021-00891-2","article-title":"Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns","volume":"53","author":"Bollen","year":"2021","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib28","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/ng.3441","article-title":"Clock-like mutational processes in human somatic cells","volume":"47","author":"Alexandrov","year":"2015","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib29","first-page":"82","article-title":"Punctuated equilibria: an alternative to phyletic gradualism","volume-title":"Models in Paleobiology","author":"Eldredge","year":"1971"},{"key":"2026020910300722300_bib30","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.aao2774","article-title":"Patient-derived organoids model treatment response of metastatic gastrointestinal cancers","volume":"359","author":"Vlachogiannis","year":"2018","journal-title":"Science"},{"key":"2026020910300722300_bib31","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13059-022-02794-9","article-title":"MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution","volume":"23","author":"Kaufmann","year":"2022","journal-title":"Genome Biol"},{"key":"2026020910300722300_bib32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41586-019-1689-y","article-title":"Pan-cancer whole-genome analyses of metastatic solid tumours","volume":"575","author":"Priestley","year":"2019","journal-title":"Nature"},{"key":"2026020910300722300_bib33","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-024-07747-9","article-title":"The genomic landscape of 2,023 colorectal cancers","volume":"633","author":"Cornish","year":"2024","journal-title":"Nature"},{"key":"2026020910300722300_bib34","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/ng.3641","article-title":"Punctuated copy number evolution and clonal stasis in triple-negative breast cancer","volume":"48","author":"Gao","year":"2016","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib35","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.cell.2018.03.043","article-title":"Deterministic evolutionary trajectories influence primary tumor growth: TRACERx renal","volume":"173","author":"Turajlic","year":"2018","journal-title":"Cell"},{"key":"2026020910300722300_bib36","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/s41588-019-0423-x","article-title":"Quantitative evidence for early metastatic seeding in colorectal cancer","volume":"51","author":"Hu","year":"2019","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib37","doi-asserted-by":"crossref","first-page":"eadg4521","DOI":"10.1126\/science.adg4521","article-title":"Oncogene-like addiction to aneuploidy in human cancers","volume":"381","author":"Girish","year":"2023","journal-title":"Science"},{"key":"2026020910300722300_bib38","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-021-03648-3","article-title":"Clonal fitness inferred from time-series modelling of single-cell cancer genomes","volume":"595","author":"Salehi","year":"2021","journal-title":"Nature"},{"key":"2026020910300722300_bib39","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1126\/science.1227670","article-title":"Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer","volume":"339","author":"Kreso","year":"2013","journal-title":"Science"},{"key":"2026020910300722300_bib40","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41573-019-0044-1","article-title":"The great escape: tumour cell plasticity in resistance to targeted therapy","volume":"19","author":"Boumahdi","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"2026020910300722300_bib41","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1136\/gutjnl-2018-316191","article-title":"Evolutionary history of human colitis-associated colorectal cancer","volume":"68","author":"Baker","year":"2019","journal-title":"Gut"},{"key":"2026020910300722300_bib42","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.cell.2019.10.026","article-title":"Clonal decomposition and DNA replication states defined by scaled single-cell genome sequencing","volume":"179","author":"Laks","year":"2019","journal-title":"Cell"},{"key":"2026020910300722300_bib43","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1186\/1471-2164-13-591","article-title":"Copynumber: efficient algorithms for single- and multi-track copy number segmentation","volume":"13","author":"Nilsen","year":"2012","journal-title":"BMC Genomics"},{"key":"2026020910300722300_bib44","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res"},{"key":"2026020910300722300_bib45","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/ng.3036","article-title":"Integrating mapping-assembly- and haplotype-based approaches for calling variants in clinical sequencing applications","volume":"46","author":"Rimmer","year":"2014","journal-title":"Nat Genet"},{"key":"2026020910300722300_bib46","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/annonc\/mdu479","article-title":"Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data","volume":"26","author":"Favero","year":"2015","journal-title":"Ann Oncol"},{"key":"2026020910300722300_bib47","doi-asserted-by":"crossref","first-page":"16910","DOI":"10.1073\/pnas.1009843107","article-title":"Allele-specific copy number analysis of tumors","volume":"107","author":"Loo","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026020910300722300_bib48","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","article-title":"The life history of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"2026020910300722300_bib49","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/bioinformatics\/bti798","article-title":"apTreeshape: statistical analysis of phylogenetic tree shape","volume":"22","author":"Bortolussi","year":"2005","journal-title":"Bioinformatics"},{"key":"2026020910300722300_bib50","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1002\/cpbi.96","article-title":"Using ggtree to visualize data on tree-like structures","volume":"69","author":"Yu","year":"2020","journal-title":"Curr Protoc Bioinformatics"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-24-0813\/3727395\/cd-24-0813.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/2\/218\/3731731\/cd-24-0813.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/2\/218\/3731731\/cd-24-0813.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T15:30:25Z","timestamp":1770651025000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/16\/2\/218\/772117\/Negative-Selection-Maintains-Grossly-Altered-but"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1,21]]},"published-print":{"date-parts":[[2026,2,6]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-24-0813","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.31276925","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276898","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276901","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296647","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276907","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276919","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296665","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296677","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296674","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296650","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296662","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276895","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276889","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276877","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276904","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276916","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276910","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276922","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296638","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296656","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296668","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296644","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296641","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296671","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276892","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276880","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276886","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276874","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.8295329","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]}}}