Fig. 1.

Clonal evolution of somatic cells is influenced by cues from the surrounding microenvironment. In the context of a normal tissue landscape, cells harboring specific mutations are likely eliminated, or their proliferation is restrained, thus contributing to the maintenance of tissue function and a tumor‐suppressive environment. On the other hand, the expansion of the same mutated clone might be promoted in the context of an altered surrounding microenvironment. The accumulation of clones harboring genetic and/or epigenetic changes might directly contribute to oncogenesis and/or to progressively establishing a tissue landscape with perturbed function. Note that this figure is likely oversimplified, and should not be interpreted to indicate that a mutant clone will never expand in a healthy tissue microenvironment, but that altered microenvironments should promote the expansion of clones with mutations that provide an adaptation to that environment. [Colour figure can be viewed at wileyonlinelibrary.com]