Melissa Q. Reeves1,2 and Allan Balmain3 1Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA 2Department of Pathology, University of Utah, Salt Lake City, Utah 84112, USA 3Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94158, USA Correspondence: Melissa.Reeveshci.utah.edu; Allan.Balmainucsf.edu

The transition from a single, initiated cell to a full-blown malignant tumor involves significant genomic evolution. Exposure to carcinogens—whether directly mutagenic or not—can drive progression toward malignancy, as can stochastic acquisition of cancer-promoting genetic events. Mouse models using both carcinogens and germline genetic manipulations have enabled precise inquiry into the evolutionary dynamics that take place as a tumor progresses from benign to malignant to metastatic stages. Tumor progression is characterized by changes in somatic point mutations and copy-number alterations, even though any single tumor can itself have a high or low burden of genomic alterations. Further, lineage-tracing, single-cell analyses and CRISPR barcoding have revealed the distinct clonal dynamics within benign and malignant tumors. Application of these tools in a range of mouse models can shed unique light on the patterns of clonal evolution that take place in both mouse and human tumors.