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dc.contributor.authorKang, Hen_US
dc.contributor.authorSalomon, MPen_US
dc.contributor.authorSottoriva, Aen_US
dc.contributor.authorZhao, Jen_US
dc.contributor.authorToy, Men_US
dc.contributor.authorPress, MFen_US
dc.contributor.authorCurtis, Cen_US
dc.contributor.authorMarjoram, Pen_US
dc.contributor.authorSiegmund, Ken_US
dc.contributor.authorShibata, Den_US
dc.date.accessioned2018-11-19T12:13:25Z
dc.date.issued2015-11en_US
dc.identifier.citationThe Journal of pathology, 2015, 237 (3), pp. 355 - 362en_US
dc.identifier.issn0022-3417en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2944
dc.identifier.eissn1096-9896en_US
dc.identifier.doi10.1002/path.4581en_US
dc.description.abstractIntratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. Here we find that ITH can be remarkably well structured by measuring point mutations, chromosome copy numbers, and DNA passenger methylation from opposite sides and individual glands of a 6 cm human colorectal adenoma. ITH was present between tumour sides and individual glands, but the private mutations were side-specific and subdivided the adenoma into two major subclones. Furthermore, ITH disappeared within individual glands because the glands were clonal populations composed of cells with identical mutant genotypes. Despite mutation clonality, the glands were relatively old, diverse populations when their individual cells were compared for passenger methylation and by FISH. These observations can be organized into an expanding star-like ancestral tree with co-clonal expansion, where many private mutations and multiple related clones arise during the first few divisions. As a consequence, most detectable mutational ITH in the final tumour originates from the first few divisions. Much of the early history of a tumour, especially the first few divisions, may be embedded within the detectable ITH of tumour genomes.en_US
dc.formatPrint-Electronicen_US
dc.format.extent355 - 362en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectHumansen_US
dc.subjectAdenomaen_US
dc.subjectColorectal Neoplasmsen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectOligonucleotide Array Sequence Analysisen_US
dc.subjectGene Expression Profilingen_US
dc.subjectDNA Mutational Analysisen_US
dc.subjectCell Divisionen_US
dc.subjectDNA Methylationen_US
dc.subjectEpigenesis, Geneticen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectGene Dosageen_US
dc.subjectPhenotypeen_US
dc.subjectPoint Mutationen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectClonal Evolutionen_US
dc.subjectBiomarkers, Tumoren_US
dc.titleMany private mutations originate from the first few divisions of a human colorectal adenoma.en_US
dc.typeJournal Article
dcterms.dateAccepted2015-06-24en_US
rioxxterms.versionofrecord10.1002/path.4581en_US
rioxxterms.licenseref.startdate2015-11en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfThe Journal of pathologyen_US
pubs.issue3en_US
pubs.notes6 monthsen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.volume237en_US
pubs.embargo.terms6 monthsen_US
icr.researchteamEvolutionary Genomics & Modellingen_US
dc.contributor.icrauthorSottoriva, Andreaen_US


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