ABSTRACT
Mutational processes in somatic cancer cell populations are constantly changing, leaving their signatures in the accumulated genomic variation in tumors. The inference of mutational signatures from the observed genetic variation enables spatiotemporal tracking of tumor mutational processes that evolve due to cellular environmental changes, mutations, and treatment regimes. Ultimately, mutational patterns illuminate the mechanistic understanding of their evolution in cancer progression. We show that the integration of cancer cell phylogeny with mutational signature deconvolution enables higher-resolution detection of gain and loss of mutational processes within the phylogeny. This approach to analyzing somatic genomic variations in 61 lung cancer patients revealed a high turn-over of mutational processes over time and closely related clonal lineages. Some mutational signatures (e.g., smoking-related) showed a higher propensity to be lost, whereas others (e.g., AID/APOBEC) were gained during lung tumors evolution. These observations shed light on the evolution of mutational processes in somatic cell evolution.
Competing Interest Statement
The authors have declared no competing interest.