PT  - JOURNAL ARTICLE
AU  - Andrea Sottoriva
AU  - Trevor A. Graham
TI  - A pan-cancer signature of neutral tumor evolution
AID  - 10.1101/014894
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 014894
4099  - http://biorxiv.org/content/early/2015/02/11/014894.short
4100  - http://biorxiv.org/content/early/2015/02/11/014894.full
AB  - 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.