Negative Selection Maintains Grossly Altered but Broadly Stable Karyotypes in Metastatic Colorectal Cancer
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. See related commentary by Okada et al., p. 192.
Authors
- Susan K. Clark (ORCID: https://orcid.org/0000-0002-6929-8082)
- Inmaculada Spiteri (ORCID: https://orcid.org/0000-0002-1097-8972)
- Nicola Valeri
- Hemant M. Kocher
- Chris Barnes
- S J Leedham
- Brendan Murphy (ORCID: https://orcid.org/0000-0003-2446-5411)
- Stuart A.C. McDonald
- Pierre Martinez
- I. Tomlinson
- William Cross (ORCID: https://orcid.org/0000-0002-4794-8777)
- Laura J. Gay (ORCID: https://orcid.org/0000-0002-6958-3254)
- Salpie Nowinski (ORCID: https://orcid.org/0000-0001-5686-3778)
- Andrea Sottoriva (ORCID: https://orcid.org/0000-0001-6709-9533)
- Ann‐Marie Baker (ORCID: https://orcid.org/0000-0001-8905-9137)
- E. Domingo
- Erika Yara-Romero (ORCID: https://orcid.org/0009-0002-7557-9128)
- Georgios Vlachogiannis (ORCID: https://orcid.org/0000-0003-3114-8772)
- Viola Walther
- Pradeep Ramagiri (ORCID: https://orcid.org/0000-0002-7677-5916)
- Hayley L. Belnoue-Davis (ORCID: https://orcid.org/0000-0003-2914-4932)
- Bingxin Lu
- Christopher Kimberley (ORCID: https://orcid.org/0000-0002-9720-4434)
- Miriam Mitchison (ORCID: https://orcid.org/0000-0003-2520-2744)
- Nik Matthews (ORCID: https://orcid.org/0000-0002-0602-1131)
- Alison Berner (ORCID: https://orcid.org/0000-0002-1132-0275)
- Marnix Jansen (ORCID: https://orcid.org/0000-0003-0645-564X)
- Morgan Moorghen (ORCID: https://orcid.org/0000-0003-0262-2674)
- Marc Williams (ORCID: https://orcid.org/0000-0001-5524-4174)
- Javier Fernández-Mateos (ORCID: https://orcid.org/0000-0002-4949-4131)
- Abhirup Banerjee (ORCID: https://orcid.org/0000-0001-9722-4470)
- Ritika Chauhan
- George Elia
- TA Graham
- A. T. Watson (ORCID: https://orcid.org/0000-0001-7052-7973)
- Frederick J.H. Whiting (ORCID: https://orcid.org/0000-0003-4090-7136)
- K. R. Smith
- Maria Traki
- Giulio Caravagna
- Lai Mun Wang
- Salvatore Milite
- Chela T. James
- Maximilian Mossner
- Darryl Shibata
- Miangela M. Laclé
- John A. Bridgewater
- Erica A. Oliveira
- Marco Novelli
- Nicholas A. Wright
- Chang-Ho Ryan Choi
- Manuel Rodriguez-Justo
- Jo-Anne Chin Aleong
- George D. Cresswell
Institutions
- Université Claude Bernard Lyon 1 (FR)
- University of Southern California (US)
- Centre National de la Recherche Scientifique (FR)
- Memorial Sloan Kettering Cancer Center (US)
- Centre for Human Genetics (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- Institute of Cancer Research (GB)
- Inserm (FR)
- Queen Mary University of London (GB)
- Barts Health NHS Trust (GB)
- Western General Hospital (GB)
- Cancer Research UK (GB)
- Edinburgh Cancer Research (GB)
- University Medical Center Utrecht (NL)
- University of Oxford (GB)
- MRC Laboratory for Molecular Cell Biology (GB)
- Whipps Cross University Hospital (GB)
- Ludwig Cancer Research (GB)
- St. Mark's Hospital (US)
- Human Technopole (IT)
- St George Hospital (AU)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Science Oxford (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Institute of Genetics (HU)
- St Mark's Hospital (GB)
- University College London (GB)
- Imperial College London (GB)
- University of Reading (GB)
- Community College of Rhode Island (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2026-01-21
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-0813
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 24.82