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• W1978214196 abstract "We previously showed that mice carrying an activated Cdk4 mutation together with melanocyte-specific mutant Hras (Cdk4R24C/R24C/TPras) develop melanoma spontaneously, but penetrance is increased and age of onset reduced after neonatal ultraviolet radiation (UVR) exposure. UVR-treated mice were more likely to develop multiple primary lesions, and these melanomas more often expressed Trp53, and less often expressed c-Myc, than melanomas from nonirradiated mice (Hacker et al., Cancer Res 2006;66:2946–52). These data suggest differences in mechanisms of tumorigenesis between melanomas developing spontaneously, or as a result of UVR exposure. To further delineate these differences, we compared global gene expression between spontaneous and UVR-induced melanomas from these mice using microarrays. We found 264 genes differentially expressed between these groups (ANOVA, p < 0.05). Selected candidate genes were validated using qRT-PCR, which confirmed upregulation of Gpr155 and Bmp7, and downregulation of Plagl1, Akap12 and Il18 in UVR-induced mouse melanomas. In humans, epidemiological studies suggest that there may be 2 predominant pathways to melanoma development. One characterized by chronic UVR exposure and which leads mainly to melanomas on sun-exposed sites; the other associated with low UVR exposure and leading predominantly to melanomas on less-exposed body sites. We found by immunohistochemical analysis that, comparing a series of human melanomas from the head (a chronically sun-exposed site; N = 82) with a set from the trunk (an intermittently exposed site; N = 65), the prevalence of IL-18 expression was significantly lower in melanomas on the head (16%) than on truncal melanomas (34%, p = 0.011). We conclude that loss of IL-18 is a marker of UVR-induced melanoma, both in animal models and humans. © 2008 Wiley-Liss, Inc." @default.
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• W1978214196 date "2008-07-01" @default.
• W1978214196 modified "2023-10-16" @default.
• W1978214196 title "Reduced expression of IL-18 is a marker of ultraviolet radiation-induced melanomas" @default.
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• W1978214196 doi "https://doi.org/10.1002/ijc.23389" @default.
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