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JJ Bosch, PW Chen, HW Mensink, MJ Jager, TG Murray, BR Ksander; Microarray Analysis of Differential Gene Expression in Autologous Primary and Metastatic Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1860.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Primary uveal melanomas are unique since they develop within an immune privileged site. A high percentage of uveal melanoma patients develop metastasis predominately in the liver. Since there are no effective therapies for metastatic tumors they are universally fatal. To gain insight into mechanisms by which primary uveal melanomas establish metastasis in the liver, we used microarray analysis to identify differentially expressed genes between a primary and metastatic uveal melanoma from the same patient. Methods:A primary uveal melanoma cell line and four metastatic uveal melanoma cell lines from the liver were established from the same patient. The primary uveal melanoma cell line was obtained directly after enucleation of the tumor-bearing eye. The metastatic uveal melanoma cell lines from the liver were obtained from four separate tumor nodules by laparoscopic biopsy. Messenger RNA was isolated from the tumor cell lines and used to synthesize cRNA, which was hybridized to Affymetrix human genome microarray chips. Differential expression of genes between the primary and individual metastatic tumor samples was analyzed using the Resolver bioinformatics analytical software. Results:: Between primary and metastatic uveal melanoma, a surprisingly small number of differentially expressed genes were identified (45/12000). The overall trend of gene expression in uveal melanomas during disease progression indicates downregulation (36/45). Ten of the 45 downregulated genes play an important role in antitumor immune responses. Proteosome subunits used in the processing of antigen peptides and LFA-6 are down regulated in metastatic uveal melanoma cells. Interestingly, Cathepsin Z that plays a key role in endosomal peptide loading of MHC Class II molecules is also downregulated. Conclusion:Our studies indicate that regulation of genes necessary for immune recognition may play an important role in the disease progression of uveal melanoma, and implies that microarray analysis provides a powerful tool to reveal important genes involved in the pathobiology of ocular tumors.
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