Clonotyping for precision oncology

•Subpopulations of cancer cells can be morphologically and/or functionally distinct.•Clonal evolution is complex and clinically relevant to disease progression, metastasis, and treatment resistance.•Intra- and inter-tumoral heterogeneity presents a significant challenge in tracking clonal evolution to guide precision medicine.•Longitudinal and temporal monitoring of clonal populations in tumor biopsies and blood plasma can improve personalized treatments.

Advances in identifying subpopulations of cancer cells and reconstructing the clonal evolution of tumors greatly enhance our understanding of the molecular events within a patient and their context relative to one another. In the rapidly unfolding era of personalized medicine, the ability to monitor clonal dynamics throughout patient care has significant clinical implications for the appropriate development or application of targeted therapies as well as understanding the potential mechanisms driving resistance. In this review, we discuss advances in biotechnology and bioinformatics that improve precision treatment by dissecting clonal evolution, focusing first on the initial discoveries in lymphomas and leukemias followed by the more recent applications to advance our understanding of prostate cancer (PCa).