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Identification of neutral tumor evolution across cancer types

Williams, MJ; Werner, B; Barnes, CP; Graham, TA; Sottoriva, A; (2016) Identification of neutral tumor evolution across cancer types. Nature Genetics , 48 (3) pp. 238-244. 10.1038/ng.3489. Green open access

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Abstract

Despite 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, selected 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.

Type: Article
Title: Identification of neutral tumor evolution across cancer types
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ng.3489
Publisher version: http://dx.doi.org/10.1038/ng.3489
Language: English
Additional information: Copyright © 2016 Macmillan Publishers Limited. All Rights Reserved.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1473744
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