A pan-cancer signature of neutral tumor evolution
Andrea Sottoriva , Trevor Graham
Despite extraordinary efforts to profile cancer genomes on a large
scale, interpreting the vast amount of genomic data in the light of
cancer evolution and in a clinically relevant manner remains
challenging. Here we demonstrate that cancer next-generation sequencing
data is dominated by the signature of growth governed by a power-law
distribution of mutant allele frequencies. The power-law signature is
common to multiple tumor types and is a consequence of the
effectively-neutral evolutionary dynamics that underpin the evolution of
a large proportion of cancers, giving rise to the abundance of
mutations responsible for intra-tumor heterogeneity. Importantly, the
law allows the measurement, in each individual cancer, of the in vivo
mutation rate and the timing of mutations with remarkable precision.
This result provides a new way to interpret cancer genomic data by
considering the physics of tumor growth in a way that is both
patient-specific and clinically relevant.
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