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Genetic basis of epithelial skin carcinomas

Costanzo, A.

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doi: 10.1097/01.cmr.0000382793.76462.06
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Basal cell carcinoma and squamous cell carcinoma, collectively termed non-melanoma skin cancers are the most common malignant tumors in humans. Basal cell carcinoma grows slowly and metastatic spread is very rare. Squamous cell carcinoma is characterized by infiltrative, destructive growth and metastasis. Long-term exposure of skin to UV light has a great impact on development of these epidermal malignancies. UV light induces cascade of events like DNA damage of keratinocytes as well as activation of proapoptotic and antiapoptotic signaling pathways. The major role in development of skin cancer is given to proapoptotic p53 tumor suppressor gene whose UV-induced mutation leads to resistance of DNA-damaged cell to apoptosis. In addition to this, basal cell carcinomas are characterized by activatory mutations in the Sonic Hedgehog-dependent pathways. Other proapoptotic molecules such as Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are strongly expressed in basal cell carcinoma and squamous cell carcinoma that could be explained by the ability of tumor to escape the attack of immune system. However, somatic mutations in tumor suppressors or oncogenes are not sufficient alone to drive cells to full transformation and to cancer progression. Epigenetic changes of chromatin, including DNA methylation and histone acetylation/methylation were recently found to give an important contribution to skin cancer progression and are target of new classes of anti cancer drugs.

© 2010 Lippincott Williams & Wilkins, Inc.