A.S. is supported by The Chris Rokos Fellowship in Evolution and Cancer.
B.W. is supported by the Geoffrey W. Lewis Post-Doctoral Training fellowship.
This work was supported by the Wellcome Trust (105104/Z/14/Z). C.P.B.
acknowledges funding from the Wellcome Trust through a Research Career
Development Fellowship (097319/Z/11/Z). This work was supported by a
Cancer Research UK Career Development Award to T.A.G. M.J.W. is supported
by a UK Medical Research Council student fellowship

Barnes, CP

Graham, TA

Sottoriva, A

Werner, B

Williams, MJ

Nature Genetics

PubMed

Marc J Williams

Benjamin Werner

Chris P Barnes

Trevor A Graham

Andrea Sottoriva

Crossref

Identification of neutral tumor evolution across cancer types

Queen Mary Research Online

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 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

Institute of Cancer Research Repository

Identification of neutral tumor evolution across cancer types.

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

UCL Discovery

https://repository.icr.ac.uk/bitstream/handle/internal/190/Identification%20of%20neutral%20tumor%20evolution%20across%20cancer%20types.pdf?sequence=2&isAllowed=y

Identification of neutral tumor evolution across cancer types

Abstract

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Crossref

Queen Mary Research Online

Institute of Cancer Research Repository

UCL Discovery