Fig. 4

A tumor evolves somatically—from initiation to detection, to resection, and to possible metastasis. New genomic mutations can confer a selective advantage to the resulting new subclone that allows it to outperform other tumor subclones (subclone competition). At the same time, the acting selection pressures can change over time (e.g., due to new subclones arising, the immune system detecting certain subclones, or as a result of therapy). Understanding such selective regimes—and how specific mutations alter a subclone’s susceptibility to changes in selection pressures—will help construct an evolutionary model of tumorigenesis. And it is only within this evolutionary model that more efficient and more patient-specific treatments can be developed. For such a model, unambiguously identifying mutation profiles of subclones via scDNA-seq of resected or biopsied single cells is crucial