Identification of neutral tumor evolution across cancer types.
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ICR Authors
Authors
Williams, MJ
Werner, B
Barnes, CP
Graham, TA
Sottoriva, A
Werner, B
Barnes, CP
Graham, TA
Sottoriva, A
Document Type
Journal Article
Date
2016-03-01
Date Accepted
2015-12-18
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 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.
Citation
Nature genetics, 2016, 48 (3), pp. 238 - 244
DOI
Rights
Source Title
Publisher
NATURE PORTFOLIO
ISSN
1061-4036
eISSN
1546-1718