"Tumor Evolution and Intratumor Heterogeneity"
All cells and their genomes are almost perfect copies of copies. Cancer and normal cells “evolve” over many decades by the multistep acquisition of multiple replication errors, which are predominately passenger mutations and epimutations. Transformation occurs when a single cell accumulates a unique combination of driver alterations. During subsequent clonal expansion and tumorigenesis, progeny of this first cancer cell acquire additional alterations, leading to intratumor heterogeneity (ITH). ITH is clinically important because variant cells are likely responsible for resistance to chemotherapy. ITH may also encode information on how human tumors grow because the topographical patterns of mutations within a tumor likely reflect its history.