Dermatopharmacology, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK.
Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK.
J Invest Dermatol. 2018 Jan;138(1):189-198. doi: 10.1016/j.jid.2017.07.844. Epub 2017 Aug 24.
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.
正常日晒皮肤含有许多表皮斑块，这些斑块 p53 蛋白染色阳性（p53 免疫阳性斑块，PIPs），被认为是皮肤癌的潜在早期前体。尽管许多 PIPs 中的 TP53 基因发生了突变，但尚不清楚 PIPs 是否含有其他与癌症相关的突变。在这里，我们报告在正常慢性暴露皮肤中，PIPs（大小主要为 <3000 个 p53 免疫阳性细胞）中存在多个在皮肤鳞状细胞癌中发生突变的基因的突变。在相应正常慢性暴露皮肤的非 PIP 表皮中未检测到这些 PIP 中的突变。尽管 PIP 中的一些这些遗传改变是克隆的，但这些病变内的许多突变是亚克隆的。在晚期癌前病变（光化性角化病和 Bowen 病）中也可见到类似的突变。我们的结果表明，慢性暴露皮肤中的 PIPs 中含有多个与癌症相关基因的突变。此外，结果表明，在晚期癌前病变和已确立的恶性肿瘤中可见到的突变的克隆进化也可能发生在正常人类皮肤的 PIPs 中。
