Identification of neutral tumor evolution across cancer types.
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Date
2016-03-01Author
Williams, MJ
Werner, B
Barnes, CP
Graham, TA
Sottoriva, A
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Clone Cells
Humans
Neoplasms
Genomics
Gene Frequency
Genetic Drift
High-Throughput Nucleotide Sequencing
Language
eng
Date accepted
2015-12-18
License start date
2016-03
Citation
Nature genetics, 2016, 48 (3), pp. 238 - 244
Publisher
NATURE PUBLISHING GROUP