Mutant clone mapping in normal oesohagus and skin
|Study ID||Alternative Stable ID||Type|
Study Datasets 2 datasets.
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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 ... (Show More)
|Illumina HiSeq 2500||866|
NOTCH1 mutant clones occupy the majority of normal human esophagus by middle age, but are comparatively rare in esophageal cancers, suggesting NOTCH1 mutations may promote clonal expansion but impede carcinogenesis. Here we test this hypothesis. Visualizing and sequencing NOTCH1 mutant clones in aging normal human esophagus, reveals frequent biallelic mutations that block NOTCH1 signaling. In mouse esophagus, heterozygous Notch1 mutation confers a competitive advantage over wild type ... (Show More)
|Illumina HiSeq 2500||63|