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Reduced expression of IL‐18 is a marker of ultraviolet radiation‐induced melanomas
Author(s) -
Hacker Elke,
Muller Konrad,
Whiteman David C.,
Pavey Sandra,
Hayward Nicholas,
Walker Graeme
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23389
Subject(s) - ultraviolet radiation , melanoma , radiation , medicine , cancer research , biology , chemistry , physics , optics , radiochemistry
We previously showed that mice carrying an activated Cdk4 mutation together with melanocyte‐specific mutant Hras ( Cdk4 R24C/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.