Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53

摘要: Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR), but the molecular mechanisms by which UVR drives melanomagenesis remain unclear. The most common somatic mutation in a V600E substitution BRAF, an early event. To investigate how accelerates oncogenic BRAF-driven melanomagenesis, we used BRAF(V600E) mouse model. In mice expressing their melanocytes, single dose of that mimicked mild sunburn humans induced clonal expansion and repeated doses increased burden. Here show sunscreen (UVA superior, UVB sun protection factor (SPF) 50) delayed onset UVR-driven melanoma, only provided partial protection. UVR-exposed tumours showed numbers nucleotide variants observed mutations (H39Y, S124F, R245C, R270C, C272G) Trp53 tumour suppressor approximately 40% cases. TP53 accepted target human non-melanoma skin cancer, not thought have major role melanoma. However, that, mice, mutant accelerated BRAF(V600E)-driven are evidence UVR-induced DNA damage Thus, provide mechanistic insight into epidemiological data linking acquired naevi humans. Furthermore, identify TP53/Trp53 as UVR-target gene cooperates with induce providing melanomagenesis. Our study validates public health campaigns promote for individuals at risk