title: Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis.
abstract: 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.
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, United Kingdom; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom; Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom bds10@cam.ac.uk.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D055088:Early Detection of Cancer; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
keywords: DNA sequencing; cancer; epidermis; stem cells