The evolutionary history of 2,658 cancers.

Cancer develops through a process of somatic evolution. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer.

Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig.

The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity.

TrackSigFreq: subclonal reconstructions based on mutation signatures and allele frequencies.

Mutational signatures are patterns of mutation types, many of which are linked to known mutagenic processes. Signature activity represents the proportion of mutations a signature generates. In cancer, cells may gain advantageous phenotypes through mutation accumulation, causing rapid growth of that subpopulation within the tumour.

The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression.

The majority of newly diagnosed prostate cancers are slow growing, with a long natural life history. Yet a subset can metastasize with lethal consequences. We reconstructed the phylogenies of 293 localized prostate tumors linked to clinical outcome data.