There is increasing interest in analysing normal non-cancer tissue for somatic mutations in cancer genes that may drive tumorigenesis in these tissues. It has previously been shown in skin and the haematopoietic system that expanded clones that carry cancer mutations exist in normal tissues, in which they accumulate with age. Seishi Ogawa and colleagues now find such mutations in normal oesophageal tissue. For example, they find expansion of clones carrying Notch mutations, which may or may not progress to oesophageal cancers. They find mutated clones from early childhood, which increase in number and size with ageing and ultimately occupy almost the entire oesophageal epithelium. They can also associate mutant clones with risk factors, such as heavy smoking and alcohol consumption.
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