Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis
Proceedings of the National Academy of Sciences
National Academy of Sciences
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Simons, B. (2015). Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis. Proceedings of the National Academy of Sciences, 113 128-133. https://doi.org/10.1073/pnas.1516123113
Using deep sequencing technology, methods based on the sporadic acquisition of somatic DNA mutations in human tissues have been used to trace the clonal evolution of progenitor cells in diseased states. However, the potential of these approaches to explore cell fate behavior of normal tissues and the initiation of preneoplasia remain underexploited. Focusing on the results of a recent deep sequencing study of eyelid epidermis, we show that the quantitative analysis of mutant clone size provides a general method to resolve the pattern of normal stem cell fate, and to detect and characterize the mutational signature of rare field transformations in human tissues, with implications for the early detection of preneoplasia.
stem cells, DNA sequencing, epidermis, cancer
We are indebted to Peter Campbell, Phil Jones and Inigo Martincorena for sharing information on the sizes of the biopsies used in their study, and for making their sequencing data publically available. We are also grateful to Trevor Graham, Philip Greulich and Anna Philpott for valuable discussions, and we acknowledge the financial support of the Wellcome Trust (grant number 098357/Z/12/Z).
WELLCOME TRUST (098357/Z/12/Z)
External DOI: https://doi.org/10.1073/pnas.1516123113
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252727
Attribution-NonCommercial 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by-nc/2.0/uk/
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