Whole Body Melanoma Transcriptome Response in XXXX .

@entity1 @entity5 @entity320 @entity7021
UNASSIGNED: The incidence of @entity320 continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent @entity320 models because fish and @entity1 melanocytes both appear in the epidermis, and fish and @entity1 @entity5 share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive @entity320 as a prelude to using transcriptome profiling to screen for drugs in a @entity7021 ( @entity7021 ) model. We generated RNA-seq data from whole body RNA isolates for controls and @entity320 fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between @entity320 and control fish; 379 of these genes were matched to @entity1 orthologs with 233 having annotated @entity1 gene symbols and 14 matched genes that contain putative deleterious variants in @entity1 @entity320 at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing @entity320 actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in @entity1 @entity320 expression studies and uncovered known and new candidate drug targets for further testing in this @entity320 @entity7021 model.
