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Sun-Induced Nonsynonymous p53 Mutations Are Extensively Accumulated and Tolerated in Normal Appearing Human Skin
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Gene Technology.
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Gene Technology.
KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
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2011 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 131, no 2, 504-508 p.Article in journal (Refereed) Published
Abstract [en]

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 similar to 35,000 new persistent protein-altering p53 mutations in sun-exposed skin of a human individual.

Place, publisher, year, edition, pages
2011. Vol. 131, no 2, 504-508 p.
Keyword [en]
basal-cell carcinoma, cancer genome, somatic mutation, human epidermis, proliferation, keratinocytes, patterns, microdissection, exposure, clones
National Category
Dermatology and Venereal Diseases
URN: urn:nbn:se:kth:diva-29718DOI: 10.1038/jid.2010.302ISI: 000286177500032ScopusID: 2-s2.0-78651405693OAI: diva2:397318
Knut and Alice Wallenberg FoundationSwedish Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 20110214Available from: 2011-02-14 Created: 2011-02-14 Last updated: 2011-12-06Bibliographically approved

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Ståhl, Patrik L.Stranneheim, HenrikBerglund, LisaLundeberg, Joakim
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Science for Life Laboratory, SciLifeLabGene TechnologyProteomics (closed 20130101)Albanova VinnExcellence Center for Protein Technology, ProNova
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Dermatology and Venereal Diseases

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