  In other words, there are very different rates, numbers and types of mutations across and within different cancer types and subtypes. Which ones matter, how, and how much, in different cancer types and subtypes, and indeed, over the course of cancer progression, is a difficult puzzle to solve. Complicating this further, a cancer may contain several subpopulations of cells (or, multiple evolving lineages), with different numbers and types of mutations within each lineage. That is, cancers have varying types and degrees of “intratumor heterogeneity.” So, samples of a tumor taken when cancer is first diagnosed may be representative of only one subpopulation of an early stage of a dynamic process. Such samples may not be representative of the genomic changes of greatest relevance to treatment-resistant late stage disease. Yet, it is late-stage disease that we need better tools to more effectively intervene upon; most cancers—if caught early—can be treated relatively effectively.