Clinical, pathologic and molecular findings in 2 Rottweiler littermates with appendicular osteosarcoma

Abstract

AbstractAppendicular osteosarcoma was diagnosed and treated in a pair of littermate Rottweiler dogs, resulting in distinctly different clinical outcomes despite similar therapy within the context of a prospective, randomized clinical trial (NCI-COTC021/022). Histopathology, immunohistochemistry, mRNA sequencing, and targeted DNA hotspot sequencing techniques were applied to both dogs’ tumors to define factors that could underpin their differential response to treatment. We describe the comparison of their clinical, histologic and molecular characteristics, as well as those from a companion cohort of Rottweiler dogs. A pan-cancer genomic sequencing panel conducted in the sibling dogs demonstrated both shared and distinct alterations in several genes implicated in osteosarcoma, including CDKN2B, SETD2, MYC, and PDGFRA, while transcriptional profiling of primary tumor tissue indicated under-expression of key immunological response genes. This report provides new insight into molecular features and potential prognostic biomarkers for canine osteosarcoma.