# Molecular Profile of Skin Cancer
## 2 UV Signature in Skin Cancer  
The role of UV light in the pathogenesis of skin cancer has been recognized since 1894 and it is believed that this external factor induces important molecular changes, the alterations in p53 gene being even considered the \"UV light signature\" on human DNA (Figure 1). However, although exposure to UV type B was directly correlated with the induction of changes in p53 expression in the skin, these changes were correlated with clinical manifestations such as local erythema, a physiological defense reaction of the skin to this type of aggression [6]. In the case of melanoma, p53 gene mutations are considered late events associated with advanced stage disease, while in non-melanocytic skin cancers (NMSC), these mutations have been identified even in premalignant lesions such as actinic keratosis (AK), which is considered to be a form of in situ squamous cell carcinoma [7]. As for the incidence of these mutations, the opinions are divided; some authors believe that they are present in 92-100% of melanomas, while others argue they are present in only 7-27%. Mutations in this gene have been found in about 66% of AK cases [8; 9]. The P16 gene is another tumor suppressor gene encoding the p16 protein, which is frequently inactivated in both melanocytic and non-melanocytic tumors [10]. Besides these two p53 and p16 genes, which have been studied for several years, other potential tumor suppressor genes were discovered very recently. A notable study conducted by [PERSON] et al. revealed the unexpected function of the protein phosphatase 2A regulatory subunit PR70 that might act as a gonosomal melanoma tumor suppressor gene [11]. Another example could be the RASA2 gene that suffers recurrent inactivating mutations in melanoma. According to [PERSON] et al. [12] RASA2, a tumor-suppressor gene that encodes a RasGAP, is mutated in 5% of melanomas. Recurrent mutations in this gene were found to increase RAS activation, melanoma cell growth and migration, while the loss of RASA2 expression was associated with reduced patient survival. Of the proto-oncogenes, we mention RAS, the first oncogene described in association with melanoma by [PERSON] et al. [13], with NRAS mutations present in about 15% of melanomas. In recent decades, the attempts to identify skin cancer-associated antigens have resulted in varying conclusions, and the immunotherapy protocols are still in development. For example, vemurafenib approved by the FDA in 2011 under the name Zelboraf is a targeted therapy obtained by the study of gene mutations occurring in the process that leads to skin cancer [14]. UV radiation has long been recognized as a risk factor for skin cancer, through its multiple effects on the skin, effects that greatly contribute to the development of neoplasia by DNA damage, induction of immunosuppression or by promoting oxidative stress. Neoplasia on photoexposed areas (head, neck) is one of the most aggressive forms, with a local recurrence rate of up to about 47% [15]. UV radiation is divided into three wavelength ranges: UVA (320-400 nm), UVB (280-320 nm) and UVC (100-280 nm). UV-A radiation crosses the stratosphere, 90-95% of it  
Figure 1: UV exposure and skin cancer. reaching the earth surface. These low-energy rays penetrate deep into the skin due to their long wavelength and lead to the occurrence of reactive oxygen species that distort the DNA; however, they are less carcinogenic than UV-B rays. The amount of UVB radiation that reaches the earth in 1-10%, but it is 100 times more mutagenic than UVA radiation. Because of its wavelength, UVB tends to damage the superficial epidermal layers, consisting of erythema, hyperpigmentation, sunburn, premature skin aging and, last but not least, carcinogenesis [16]. The process of carcinogenesis arises from oxidative stress and/or DNA damage or translational gene mutation type. Both UV-A and UV-B can cause local immunosuppression by reducing the antigen-presenting cells or by increasing the production of immunosuppressive cytokines.