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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens.

PURPOSE: Downregulation of melanoma-associated antigens (MAAs), against which natural cytolytic T lymphocytes (CTLs) exist in humans, is one of the mechanisms that aids in evasion of immune surveillance. In view of putative re-expression strategies for MAAs during immunotherapy, this study was conducted to investigate MAA silencing in malignant melanoma. METHODS: The expression of the MAA Melan-A/MART-1 was analyzed in 10 uveal and 10 cutaneous patient-derived melanoma cell lines by Western blot analysis and RT-PCR. Expression characteristics of four other MAAs-Tyr, Tyrp1, Dct, and gp100/Pmel17-were analyzed by RT-PCR. DNA methylation patterns at the Melan-A/MART-1 promoter region were investigated by methylation-sensitive restriction enzyme digestion and subsequent Southern blot analysis. Exogenous promoter activity was assessed in all 20 melanoma cell lines to correlate the DNA methylation patterns with Melan-A/MART-1 expression. RESULTS: MAA expression was observed in 15 of the 20 melanoma cell lines. Furthermore, there is a direct correlation between DNA methylation patterns at the Melan-A/MART-1 promoter region, exogenous Melan-A/MART-1 promoter activity, and Melan-A/MART-1 protein expression. These data reveal the division of patient-derived melanoma cell lines into two distinct subsets, which are identical for both uveal and cutaneous tumor types. CONCLUSIONS: The authors propose a categorization of melanoma cell lines into two different panels based on shared MAA-expression characteristics: panel I, MAA-expressing cell lines, and panel II, MAA-deficient cell lines. This categorization can be used to obtain knowledge about the regulation of MAA-expression and for further research concerning MAA-based immunotherapy.[1]


  1. Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens. van Dinten, L.C., Pul, N., van Nieuwpoort, A.F., Out, C.J., Jager, M.J., van den Elsen, P.J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
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