The evolving mutational landscape of normal human esophagus

Dataset ID Technology Samples
EGAD00001004158 Illumina HiSeq 2500 N/A

Dataset Description

The extent to which cells in normal tissues accumulate mutations during life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors aged 20-75. Somatic mutations accumulate with age and are mainly caused by intrinsic mutational processes. We found strong Darwinian selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of such clones per square centimeter. By middle age, clones with cancer-associated mutations cover most of the epithelium, with NOTCH1 and TP53 mutations affecting 40% and 10% of all cells, respectively. Remarkably, the prevalence of NOTCH1 mutations in normal esophagus is several times higher than in esophageal cancers. The esophagus emerges as an evolving patchwork of mutant clones that colonize the majority of the epithelium, with implications for our understanding of cancer and ageing.

Data Use Conditions


See further information on Data Use Conditions

Label Code Version Modifier
general research use DUO:0000042 2021-02-23
institution specific restriction DUO:0000028 2021-02-23
publication required DUO:0000019 2021-02-23
user specific restriction DUO:0000026 2021-02-23