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dc.contributor.authorWilliams, MJ
dc.contributor.authorWerner, B
dc.contributor.authorBarnes, CP
dc.contributor.authorGraham, TA
dc.contributor.authorSottoriva, A
dc.date.accessioned2016-10-26T16:36:01Z
dc.date.issued2016-03
dc.identifier.citationNature genetics, 2016, 48 (3), pp. 238 - 244
dc.identifier.issn1061-4036
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/190
dc.identifier.eissn1546-1718
dc.identifier.doi10.1038/ng.3489
dc.description.abstractDespite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power law fits with high precision 323 of 904 cancers from 14 types and from different cohorts. In malignancies identified as evolving neutrally, all clonal selection seemingly occurred before the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intratumoral heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intratumoral heterogeneity.
dc.formatPrint-Electronic
dc.format.extent238 - 244
dc.languageeng
dc.language.isoeng
dc.subjectClone Cells
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectGenomics
dc.subjectGene Frequency
dc.subjectGenetic Drift
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.titleIdentification of neutral tumor evolution across cancer types.
dc.typeJournal Article
dcterms.dateAccepted2015-12-18
rioxxterms.versionofrecord10.1038/ng.3489
rioxxterms.licenseref.startdate2016-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature genetics
pubs.issue3
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume48
pubs.embargo.termsNo embargo
dc.contributor.icrauthorSottoriva, Andreaen


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