Deciphering Genetic Intratumor Heterogeneity and Its Impact on Cancer Evolution

Abstract

Cancer is a disease reliant on the generation of mutations and the subsequent selection of those subpopulations endowed with the greatest fitness advantage. Beginning with a heterogeneous landscape of somatic alterations, various selective pressures acting on a tumor can shape the way it evolves. In this review, we first discuss the current bioinformatics tools available to tease apart the heterogeneous nature of a tumor and second consider the impact that evolutionary forces have on sculpting a tumor. Neighboring subclones may alter the microenvironment cultivating either cooperation or competition between clonal populations. Additionally, the harsh environment brought about by therapy and the immune system may force adaptation. Finally, we examine recent analyses focused on precancerous samples, which help to reveal clonal selection occurring during the earliest stages of tumor development, as well as work that has identified patterns of somatic evolution observed in normal tissues.