02768: Defining the Functional Consequences and Therapeutic Vulnerability of Dystrophin Alterations in Canine Osteosarcoma

One Health: Yes

Abstract

Osteosarcoma is the most common primary bone tumor in dogs, predominantly occurring in large and giant breed dogs such as the Great Dane, Irish Wolfhound, Rottweiler, Greyhound and Golden Retriever, among others. While surgery and chemotherapy help improve outcome for patients, over 90% of dogs will develop chemotherapy resistance and die due to disease progression within one year. Therefore, new treatment approaches are needed for dogs with osteosarcoma. The investigators previously performed whole genome sequencing of canine osteosarcoma tumors and identified large deletions in DMD, the gene that encodes the dystrophin protein. Loss of this protein is associated with more aggressive cancers in people, however virtually nothing is known about the role of dystrophin in canine osteosarcoma. This study will determine the incidence of DMD gene deletions across a larger number of osteosarcoma tumors and validate a targeted sequencing panel to rapidly identify these deletions in client-owned dogs with osteosarcoma. Additionally, the investigators will characterize the role of DMD deletions in tumor biology to determine the best way to treat osteosarcoma tumors with DMD deletions. This work will lay the groundwork for future prospective clinical trials targeting genetic mutations in dogs with osteosarcoma.

Publication(s)

Megquier, K., Turner-Maier, J., Morrill, K., Li, X., Johnson, J., Karlsson, E. K., London, C. A., & Gardner, H. L. (2022). The genomic landscape of canine osteosarcoma cell lines reveals conserved structural complexity and pathway alterations. PLOS ONE, 17(9), e0274383. https://doi.org/10.1371/journal.pone.0274383