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Sun-Induced Nonsynonymous p53 Mutations Are Extensively Accumulated and Tolerated in Normal Appearing Human Skin

Division of Gene Technology, Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden.
Journal of Investigative Dermatology (Impact Factor: 6.37). 10/2010; 131(2):504-8. DOI: 10.1038/jid.2010.302
Source: PubMed

ABSTRACT Here we demonstrate that intermittently sun-exposed human skin contains an extensive number of phenotypically intact cell compartments bearing missense and nonsense mutations in the p53 tumor suppressor gene. Deep sequencing of sun-exposed and shielded microdissected skin from mid-life individuals revealed that persistent p53 mutations had accumulated in 14% of all epidermal cells, with no apparent signs of a growth advantage of the affected cell compartments. Furthermore, 6% of the mutated epidermal cells encoded a truncated protein. The abundance of these events, not taking into account intron mutations and mutations in other genes that also may have functional implications, suggests an extensive tolerance of human cells to severe genetic alterations caused by UV light, with an estimated annual rate of accumulation of ∼35,000 new persistent protein-altering p53 mutations in sun-exposed skin of a human individual.

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Available from: Patrik L Ståhl, Sep 01, 2014
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    • "A recent deep sequencing study reveals 14% of human basal cells in sun exposed sites carry a p53 coding exon mutation, consistent with earlier immunostaining results (Jonason et al. 1996; Stahl et al. 2011). These observations argue that a very small proportion of cells in PMC evolve in to tumors (de Gruijl 2008; Stahl et al. 2011). A major factor contributing to scarcity of PMC progression is the low probability of mutant progenitors acquiring the additional mutations required for malignant transformation. "
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