Transcriptional landscape in BRAF wild type metastatic melanoma

Abstract

AbstractMelanoma is a relative rare disease worldwide, nevertheless it has a great relevance in some countries such as in Europe. In order to shed some light upon the transcriptional profile of skin melanoma, we compared the gene expression of 6 independent tumours (all progressed towards metastatic disease and with wild type BRAF) to the expression profile of healthy melanocytes. Paraffin-embedded samples were manually microdissected to obtain enriched samples and then RNA was extracted and analysed through a microarray-based approach. An exhaustive bioinformatics analysis was performed to identify differentially expressed transcripts between the two groups as well as enriched functional terms. Overall, 50 up- and 19 down-regulated transcripts were found to be significantly changed in tumour compared to control tissue. Among the upregulated transcripts, the majority belonged to the immune response group and to proteasome, while most of the downregulated genes were related to cytosolic ribosomes. Interestingly, Gene Set Enrichment Analysis (GSEA), along with the analysis of the expression data retrieved from TCGA/GTEx databases, confirmed the general trend of downregulation affecting cytoribosome proteins. In contrast, transcripts coding for mitori-bosome proteins showed the opposite trend.