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Significance The sporadic acquisition of somatic DNA mutation confers a hereditary label that can be used to trace the fate behavior of cells in normal and diseased states. Applied to human tumor samples, DNA deep sequencing methods have revealed the landscape of somatic mutations and have identified a repertoire of genes implicated in cancer. By adapting statistical methods used to analyze lineage tracing data in transgenic animal models, we use the example of epidermis to show how deep sequencing data can provide quantitative insight into the self-renewal properties of normal human tissues and can serve as a platform to define rare nonneutral field transformations.

Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis