Resolving genetic heterogeneity in cancer

To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and cancer genomics approaches are driving new insights into cancer evolutionary patterns in time and space. In contrast to species evolution, cancer is a particular case owing to the vast size of tumour cell populations, chromosomal instability and its potential for phenotypic plasticity. Nevertheless, an evolutionary framework is a powerful aid to understand cancer progression and therapy failure. Indeed, such a framework could be applied to predict individual tumour behaviour and support treatment strategies. Recent next-generation sequencing studies have captured the spatial and temporal evolutionary patterns that shape cancer. This Review provides an overview of the theoretical models of tumour evolution and discusses what to consider when inferring evolutionary dynamics from genomic data.