{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["634(8036)"],"submitter":["Sadien ID"],"pubmed_abstract":["Loss-of-function mutations in the tumour suppressor APC are an initial step in intestinal tumorigenesis<sup>1,2</sup>. APC-mutant intestinal stem cells outcompete their wild-type neighbours through the secretion of Wnt antagonists, which accelerates the fixation and subsequent rapid clonal expansion of mutants<sup>3-5</sup>. Reports of polyclonal intestinal tumours in human patients and mouse models appear at odds with this process<sup>6,7</sup>. Here we combine multicolour lineage tracing with chemical mutagenesis in mice to show that a large proportion of intestinal tumours have a multiancestral origin. Polyclonal tumours retain a structure comprising subclones with distinct Apc mutations and transcriptional states, driven predominantly by differences in KRAS and MYC signalling. These pa"],"journal":["Nature"],"pagination":["1196-1203"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11525183"],"repository":["biostudies-literature"],"pubmed_title":["Polyclonality overcomes fitness barriers in Apc-driven tumorigenesis."],"pmcid":["PMC11525183"],"pubmed_authors":["Sadien ID","Bailey S","Couturier DL","Adler S","Kemp R","Lourenco FC","Adams DJ","Winton DJ","Mehmed S","Sawle A","Eldridge M"],"additional_accession":[]},"is_claimable":false,"name":"Polyclonality overcomes fitness barriers in Apc-driven tumorigenesis.","description":"Loss-of-function mutations in the tumour suppressor APC are an initial step in intestinal tumorigenesis<sup>1,2</sup>. APC-mutant intestinal stem cells outcompete their wild-type neighbours through the secretion of Wnt antagonists, which accelerates the fixation and subsequent rapid clonal expansion of mutants<sup>3-5</sup>. Reports of polyclonal intestinal tumours in human patients and mouse models appear at odds with this process<sup>6,7</sup>. Here we combine multicolour lineage tracing with chemical mutagenesis in mice to show that a large proportion of intestinal tumours have a multiancestral origin. Polyclonal tumours retain a structure comprising subclones with distinct Apc mutations and transcriptional states, driven predominantly by differences in KRAS and MYC signalling. These pa","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-07-16T03:08:28.514Z","creation":"2025-04-06T15:31:57.443Z"},"accession":"S-EPMC11525183","cross_references":{"pubmed":["39478206"],"doi":["10.1038/s41586-024-08053-0"]}}