Somatic mutation: What shapes the mutational landscape of normal epithelia?

Abstract Epithelial stem cells accumulate mutations throughout life. Some of these mutants increase competitive fitness and may form clones that colonize the stem cell niche and persist to acquire further genome alterations. After a transient expansion, mutant stem cells must revert to homeostatic behavior so normal tissue architecture is maintained. Some positively selected mutants may promote cancer development while others inhibit carcinogenesis. Factors that shape the mutational landscape include wild type and mutant stem cell dynamics, competition for the niche, and environmental exposures. Understanding these processes may give new insight into the basis of cancer risk and opportunities for cancer prevention.