Somatic mutant clones colonize the human esophagus with age

The mutational burden of aging As people age, they accumulate somatic mutations in healthy cells. About 25% of cells in normal, sun-exposed skin harbor cancer driver mutations. What about tissues not exposed to powerful mutagens like ultraviolet light? Martincorena et al. performed targeted gene sequencing of normal esophageal epithelium from nine human donors of varying age (see the Perspective by Chanock). The mutation rate was lower in esophagus than in skin, but there was a strong positive selection of clones carrying mutations in 14 cancer-associated genes. By middle age, more than half of the esophageal epithelium was colonized by mutant clones. Interestingly, mutations in the cancer driver gene NOTCH1 were more common in normal esophageal epithelium than in esophageal cancer. Science , this issue p. 911 ; see also p. 893