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Ronald Tongbai, Jennifer Vargas, Gintien Huang, Bradley Straatsma; Transcriptional Regulatory Network Analysis of Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):170. doi: https://doi.org/.
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Uveal melanoma is the most common form of intraocular melanoma in adults and metastasis to the liver and lungs is associated with a worse prognosis. A study by Onken et al utilized microarrays to characterize the gene expression profiles of tumors which metastasized and compared them with the gene expression profiles of tumors which did not metastasize. The study identified specific genetic signatures which discriminated between tumors that do and do not metastasize. The study provides an important insight into the molecular pathways and biological processes that govern the establishment and growth of these metastases.
Promoter region sequences from a 600 bp region (-500 bp upstream to +100 bp downstream) were obtained for each gene in each of the gene lists using the ProSpector free web-based promoter annotation tool (4). The promoter regions of each of the gene signatures were analyzed for matches to approximately 300 position weight matrices (TFBS) using the MatInspector module of the GEMS LauncheR 4.1 (Genomatix, Munich, Germany).
A regulatory profile was generated based on the methods described above. Each of the gene lists were analyzed to generate p-values representing the degree of statistical enrichment for each of the approximately 300 TFBS in the promoter regions of these genes as described in the methods.
These results provide an important insight into the cell biology that governs the regulatory networks involved in uveal melanoma. Transcription factors implicated in the cell biology of uveal melanoma include AP2, ATF, and MapK/ERK.
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