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Subclonal Evolution of Cancer-Related Gene Mutations in p53 Immunopositive Patches in Human Skin
Ist Teil von
Journal of investigative dermatology, 2018-01, Vol.138 (1), p.189-198
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2018
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Normal sun-exposed skin contains numerous epidermal patches that stain positive for p53 protein (p53 immunopositive patches, PIPs), which are considered potential early precursors of skin cancer. Although the TP53 gene is mutated in many PIPs, it is unclear whether PIPs contain any other cancer-related mutations. Here we report that PIPs, predominantly <3,000 p53 immunopositive cells in size, within normal chronically exposed skin contain mutations in multiple genes that are mutated in cutaneous squamous cell cancers. These mutations in the PIPs were not detected within the non-PIP epidermis of corresponding normal chronically exposed skin. Although some of these genetic alterations are clonal in the PIPs, many of the mutations are subclonal within these lesions. Similar mutations are seen in later precancers (actinic keratoses and Bowen’s disease). Our results demonstrate that PIPs in chronically exposed skin contain multiple mutations in cancer-related genes. In addition, the results indicate that the clonal evolution of mutations that are seen within later precancerous lesions and in established malignancy can also occur in PIPs within normal human skin.
Sprache
Englisch
Identifikatoren
ISSN: 0022-202X
eISSN: 1523-1747
DOI: 10.1016/j.jid.2017.07.844
Titel-ID: cdi_proquest_miscellaneous_1933232129
Format
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