As we age, mutations accumulate in healthy esophageal tissue
As we age, many mutations occur in the esophagus.
Scientists from the MRC Cancer Unit of Wellcome Sanger Institute, as well as other departments of University of Cambridge, discovered that the number of mutations in healthy esophageal tissues increases with age. By the time they reach middle age, the tissue is more likely to have a specific mutation than it does without it.
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It is not well understood how many mutations cells accumulate in normal tissues over the course of their lives. Genome sequencing can detect clones of mutant cells. We identified mutant clones within normal esophageal tissue from nine donors (ranging in age from 20 to 75). Somatic mutations increased with age, and were primarily caused by intrinsic mutational processes. We observed a strong selection of clones with mutations in fourteen cancer genes. There were tens or hundreds of clones on a square centimeter. Clones with cancer-associated mutants were found in the epithelium of middle-aged and older donors. NOTCH1 mutations affected 12 to 80% of cells and TP53 mutations 2 to 37%. The prevalence of NOTCH1 mutants in the normal esophagus is several times greater than that in cancerous esophageal tissue. These findings are important for understanding cancer and aging.