Melanoma is one of the most aggressive malignancies of the skin. The genetic composition of melanoma is complex and varies among different subtypes. With the aid of recent technologies such as next generation sequencing and single-cell sequencing, our understanding of the genomic landscape of melanoma and its tumor microenvironment has become increasingly clear. These advances may provide explanation to the heterogenic treatment outcomes of melanoma patients under current therapeutic guidelines and provide further insights to the development of potential new therapeutic targets. Here, we provide a comprehensive review on the genetics related to melanoma tumorigenesis, metastasis, and prognosis. We also review the genetics affecting the melanoma tumor microenvironment and its relation to tumor progression and treatment.

Solar radiation is essential for life on Earth but is also a major contributor to skin carcinogenesis. Solar radiation, particularly ultraviolet (UV) B (280–320 nm) and UVA (320–400 nm), induces photocarcinogenesis via various pathways. UV light can directly cause DNA damage, resulting in genetic mutations if not repaired correctly. UV light can also induce photocarcinogenesis by generating reactive oxygen species, inducing immunosuppression and inflammation. Recently, visible light (400–760 nm) has been shown to contribute to photocarcinogenesis by activating oxidative pathways. In addition to the irradiation dose (fluence, J/m²), UVB irradiance (W/m²) is also considered a factor influencing photocarcinogenesis. In this review, we summarize the mechanisms of photocarcinogenesis and provide strategies to prevent skin cancer.

Background: How different tools for evaluating health-related quality of life (QoL) reflect the burden of vitiligo has rarely been compared. In this study, we aim to evaluate the impact of vitiligo on QoL using currently available tools. Methods: A single-center, cross-sectional study of vitiligo patients was performed. QoL was evaluated using the dermatology life quality index (DLQI), short form-36 (SF-36), and willingness to pay (WTP). As the original DLQI cutoff score (>10) indicating aginificantly impated QoL was found to underestimate QoL, receiver operating characteristic (ROC) curve was use to determine a new cutoff point discriminating vitiligo patients with positive mental stress (SF-36 mental health ≤ 52). Results: Of the 143 patients enrolled, 24.5% were identified having significant mental stress by SF-36 mental health domain score ≤ 52 while there were only 13.3% patients with significantly hampered QoL indicated by DLQI >10. Using ROC analysis, DLQI ≥ 7 was found to be a more appropriate DLQI cutoff value for identifying mental stress in vitiligo patients. Additionally, the median WTP for treating vitiligo was comparable to other inflammatory skin diseases. Conclusions: There exist discrepancies in the outcomes identifying significant disease burden of vitiligo using DLQI and SF-36, making the current DLQI cutoff score (>10) for identifying significantly affected QoL inappropriate for these patients.

Phototherapy is the most commonly used modality for repigmenting vitiligo. Currently, UVB emitting devices, including narrow band UVB (NBUVB) and excimer laser/light, are considered as the treatment of choice. While emitting wavelengths at close proximity, excimer lights emit higher irradiance (HI; W/m²) compared to NBUVB. Clinical reports have shown that excimer light is more efficacious in treating vitiligo compared to NBUVB, and we demonstrated that irradiance plays a critical role in promoting melanoblasts differentiation. UVB radiation from the sun is closely associated with photocarcinogenesis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance (low irradiance (LI) UVB). Sunscreen use was associated with skin cancer reduction in clinical trials. Paradoxically, sunscreen use was associated with increased sunburn episodes in the real‐world settings. It was shown that UVB‐induced sunburn depends on fluence (J/m²) but not irradiance of UVB radiation. We investigated the significance of irradiance in the context of UVB‐induced carcinogenesis of the skin. For mice receiving equivalent fluence of UVB exposure, the LIUVB treated mice showed earlier tumor development, larger tumor burden, and more epidermal keratinocytes harboring mutant p53 as compared to their HIUVB‐treated counterparts. These results suggested that at equivalent fluence, LIUVB radiation has more photocarcinogenic potential on the skin compared to its HI counterpart. Since development of sunburn with or without sunscreen use indicates that certain threshold of UVB fluence has been received by the skin at LI and HI, respectively, sunburn episodes with sunscreen use (LIUVB) is more damaging to the skin compared to that without sunscreen (HIUVB) application. In summary, since irradiance plays an important role determining the biological effects of UVB radiation on the skin, future related studies should take this critical parameter into consideration.