Gene Expression Profiling Identifies Inflammation and Angiogenesis as Distinguishing Features of Canine Hemangiosarcoma

The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. We first evaluated mutational events in candidate genes that might drive hemangiosarcoma. Each of 10 tumor and four non-tumor samples had wild type sequence for these genes. Thus, we used gene expression profiling as a global approach to test the hypothesis. Hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on robust signatures that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. The data do not distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that the cells that give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine 10 dogs with hemangiosarcoma were compared to 3 dogs without hemangiosarcoma and 21 dogs with other tumors