Genome-wide analysis of hemangiosarcoma tumor tissue using ChRO-seq finds ECM remodeling plays an important role in canine hemangiosarcoma pathogenesis.

Canine hemangiosarcoma (HSA) is an aggressive vascular tumor that arise from malignant endothelial cells. To gain deeper understanding of HSA pathogenesis, we performed Chromatin-Run-On sequencing (ChRO-seq) experiment on 17 HSA tumor tissues and 4 normal tissue. ChRO-seq analysis revealed over a thousand differentially expressed genes in HSA tissue compared with normal splenic tissue (FDR <0.005). Interestingly the majority of genes overexpressed in HSA tumor tissue were associated with extracellular matrix (ECM) remodeling. This observation correlated well with our histological analysis, which found that HSA tumors contain a rich and complex collagen network. Additionally, we characterized the protein expression patterns of two highly overexpressed molecules identified in ChRO-seq analysis, podoplanin (PDPN) and laminin alpha 4 (LAMA4). We found that the expression of these two ECM-associated factors appeared to be largely limited to transformed endothelial cells within the HSA lesions. Outcomes from this study suggest that ECM remodeling has an important role in HSA pathogenesis. Overall design: ChRO-seq was used to analyze canine splenic hemangiosarcoma tissues and normal splenic tissues.