{"entity": "researcher", "timestamp": "2026-08-20T20:45:36.979Z", "family": "Barnes", "given": "Chris P", "initials": "CP", "orcid": "0000-0002-9459-1395", "affiliations": ["Department of Cell and Developmental Biology, University College London, London, UK."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1368b46b87f4bf8a3aa1aceeb6be67c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1368b46b87f4bf8a3aa1aceeb6be67c"}}, "publications": [{"entity": "publication", "iuid": "700c9c9b77f947918df55a48e36934ae", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/700c9c9b77f947918df55a48e36934ae.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/700c9c9b77f947918df55a48e36934ae"}}, "title": "Fluctuating DNA methylation tracks cancer evolution at clinical scale.", "authors": [{"family": "Gabbutt", "given": "Calum", "initials": "C", "orcid": "0000-0003-1946-4780", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48f547a4c7484325a311da6e553a0247.json"}}, {"family": "Duran-Ferrer", "given": "Mart\u00ed", "initials": "M", "orcid": "0000-0003-1666-5819", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf156c05415b4ca68ef16154910405e8.json"}}, {"family": "Grant", "given": "Heather E", "initials": "HE", "orcid": "0000-0001-9500-1644", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06744ddc44d748f1894b065419de8ad0.json"}}, {"family": "Mallo", "given": "Diego", "initials": "D", "orcid": "0000-0002-9046-8859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d97634551f74da2b29a56142551a8c2.json"}}, {"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50c437deb106439282f36834216b320a.json"}}, {"family": "Househam", "given": "Jacob", "initials": "J", "orcid": "0000-0003-3199-336X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21e8fbb71de94c00862397e105da9408.json"}}, {"family": "Villamor", "given": "Neus", "initials": "N", "orcid": "0000-0001-6538-4111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fd7ec1d572b4b7b9998008a868ed898.json"}}, {"family": "M\u00fcller", "given": "Madlen", "initials": "M", "orcid": "0000-0002-1381-7517", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d8b297dc31b34418acf97fd4daec1fb3.json"}}, {"family": "Heath", "given": "Simon", "initials": "S"}, {"family": "Raineri", "given": "Emanuele", "initials": "E"}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ee07e408e24eefa23105dcc6aa252b.json"}}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13160825496147c897b8d57be3a61caa.json"}}, {"family": "Gut", "given": "Ivo G", "initials": "IG", "orcid": "0000-0001-7219-632X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30b9984db1b749e2967f28dc9b631c20.json"}}, {"family": "Campo", "given": "Elias", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ab2ad72e7442da10e441a24100503.json"}}, {"family": "Lopez-Guillermo", "given": "Armando", "initials": "A"}, {"family": "Fitzgibbon", "given": "Jude", "initials": "J"}, {"family": "Barnes", "given": "Chris P", "initials": "CP", "orcid": "0000-0002-9459-1395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1368b46b87f4bf8a3aa1aceeb6be67c.json"}}, {"family": "Shibata", "given": "Darryl", "initials": "D", "orcid": "0000-0002-4567-1639", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87bcf54a472b47c18161607a2e4acba1.json"}}, {"family": "Martin-Subero", "given": "Jos\u00e9 I", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6b1944a98214848b864342473012567.json"}}, {"family": "Graham", "given": "Trevor A", "initials": "TA", "orcid": "0000-0001-9582-1597", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/01095c73ab804c6b8a3d777973a84e86.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "645", "issue": "8081", "pages": "764-773", "issn-l": "0028-0836"}, "abstract": "Cancer development and response to treatment are evolutionary processes1,2, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging3. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time4, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types. We measure that subclonal selection occurs only infrequently within bulk samples and detect occasional examples of multiple independent primary tumours. Clinically, we observe faster initial tumour growth in more aggressive disease subtypes, and that evolutionary histories are strong independent prognostic factors in two series of chronic lymphocytic leukaemia. Using EVOFLUx for phylogenetic analyses of aggressive Richter-transformed chronic lymphocytic leukaemia samples detected that the seed of the transformed clone existed decades before presentation. Orthogonal verification of EVOFLUx inferences is provided using additional genetic data, including long-read nanopore sequencing, and clinical variables. Collectively, we show how widely available, low-cost bulk DNA methylation data precisely measure cancer evolutionary dynamics, and provides new insights into cancer biology and clinical behaviour.", "doi": "10.1038/s41586-025-09374-4", "pmid": "40931062", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12443617"}, {"db": "pii", "key": "10.1038/s41586-025-09374-4"}], "notes": [], "created": "2026-08-20T08:59:16.174Z", "modified": "2026-08-20T08:59:16.679Z"}, {"entity": "publication", "iuid": "146d1af65d564cb7b14832b3d89bf122", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/146d1af65d564cb7b14832b3d89bf122.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/146d1af65d564cb7b14832b3d89bf122"}}, "title": "Evolutionary dynamics of 1,976 lymphoid malignancies predict clinical outcome", "authors": [{"family": "Gabbutt", "given": "Calum", "initials": "C", "orcid": "0000-0003-1946-4780", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48f547a4c7484325a311da6e553a0247.json"}}, {"family": "Duran-Ferrer", "given": "Mart\u00ed", "initials": "M", "orcid": "0000-0003-1666-5819", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf156c05415b4ca68ef16154910405e8.json"}}, {"family": "Grant", "given": "Heather", "initials": "H", "orcid": "0000-0001-9500-1644", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06744ddc44d748f1894b065419de8ad0.json"}}, {"family": "Mallo", "given": "Diego", "initials": "D", "orcid": "0000-0002-9046-8859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d97634551f74da2b29a56142551a8c2.json"}}, {"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50c437deb106439282f36834216b320a.json"}}, {"family": "Househam", "given": "Jacob", "initials": "J", "orcid": "0000-0003-3199-336X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21e8fbb71de94c00862397e105da9408.json"}}, {"family": "Villamor", "given": "Neus", "initials": "N", "orcid": "0000-0001-6538-4111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fd7ec1d572b4b7b9998008a868ed898.json"}}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ee07e408e24eefa23105dcc6aa252b.json"}}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13160825496147c897b8d57be3a61caa.json"}}, {"family": "Campo", "given": "Elias", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ab2ad72e7442da10e441a24100503.json"}}, {"family": "Lopez-Guillermo", "given": "Armando", "initials": "A", "orcid": "0000-0002-8588-8381", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9850101afe4949fea16879b1f1bf8920.json"}}, {"family": "Fitzgibbon", "given": "Jude", "initials": "J", "orcid": "0000-0002-9069-1866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/24b166a943ce431f8245441b452ad7ed.json"}}, {"family": "Barnes", "given": "Chris P", "initials": "CP", "orcid": "0000-0002-9459-1395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1368b46b87f4bf8a3aa1aceeb6be67c.json"}}, {"family": "Shibata", "given": "Darryl", "initials": "D", "orcid": "0000-0002-4567-1639", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87bcf54a472b47c18161607a2e4acba1.json"}}, {"family": "Martin-Subero", "given": "Jos\u00e9 I", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6b1944a98214848b864342473012567.json"}}, {"family": "Graham", "given": "Trevor A", "initials": "TA", "orcid": "0000-0001-9582-1597", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/01095c73ab804c6b8a3d777973a84e86.json"}}], "type": "posted-content", "published": "2023-11-10", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2023.11.10.23298336", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:48:54.694Z", "modified": "2026-08-20T10:49:37.628Z"}, {"entity": "publication", "iuid": "8e47eaad95d44fd58e14fea9ad06b70c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8e47eaad95d44fd58e14fea9ad06b70c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8e47eaad95d44fd58e14fea9ad06b70c"}}, "title": "Deterministic evolution and stringent selection during preneoplasia.", "authors": [{"family": "Karlsson", "given": "Kasper", "initials": "K"}, {"family": "Przybilla", "given": "Moritz J", "initials": "MJ", "orcid": "0000-0001-5645-9492", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dec82740d4e449cab71851de8ef7d40f.json"}}, {"family": "Kotler", "given": "Eran", "initials": "E", "orcid": "0000-0002-1463-7462", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bb6d59ac39c4ea88c991dc7de42c305.json"}}, {"family": "Khan", "given": "Aziz", "initials": "A", "orcid": "0000-0002-6459-6224", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f34f17ef9f3b441cab25c31169bf9764.json"}}, {"family": "Xu", "given": "Hang", "initials": "H"}, {"family": "Karagyozova", "given": "Kremena", "initials": "K"}, {"family": "Sockell", "given": "Alexandra", "initials": "A"}, {"family": "Wong", "given": "Wing H", "initials": "WH"}, {"family": "Liu", "given": "Katherine", "initials": "K", "orcid": "0000-0002-9616-9403", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a71fb7261bb2496abf12ec961ca875ce.json"}}, {"family": "Mah", "given": "Amanda", "initials": "A"}, {"family": "Lo", "given": "Yuan-Hung", "initials": "YH"}, {"family": "Lu", "given": "Bingxin", "initials": "B", "orcid": "0000-0002-0606-5150", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50fce7a2869a46e2bf66df3106dd7678.json"}}, {"family": "Houlahan", "given": "Kathleen E", "initials": "KE"}, {"family": "Ma", "given": "Zhicheng", "initials": "Z"}, {"family": "Suarez", "given": "Carlos J", "initials": "CJ"}, {"family": "Barnes", "given": "Chris P", "initials": "CP", "orcid": "0000-0002-9459-1395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1368b46b87f4bf8a3aa1aceeb6be67c.json"}}, {"family": "Kuo", "given": "Calvin J", "initials": "CJ", "orcid": "0000-0002-7427-5985", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7ac6e9f833a4fb3b64e9b147771b9bb.json"}}, {"family": "Curtis", "given": "Christina", "initials": "C", "orcid": "0000-0003-0166-3802", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2f41023e26414160b548610761c16452.json"}}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "618", "issue": "7964", "pages": "383-393", "issn-l": "0028-0836"}, "abstract": "The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours.", "doi": "10.1038/s41586-023-06102-8", "pmid": "37258665", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10247377"}, {"db": "pii", "key": "10.1038/s41586-023-06102-8"}], "notes": [], "created": "2026-08-20T08:58:36.141Z", "modified": "2026-08-20T08:58:36.506Z"}]}