Osteosarcoma

Human-Canine Genetic Similarities

Research looks at osteosarcoma in dogs and children

Osteosarcoma, a deadly bone cancer, is genetically similar in dogs and human children, according to a study by Tufts University and the Translational Genomics Research Institute (TGen) recently published in Communications Biology. The findings could help break the logjam in the treatment of this disease, which hasn't seen a significant medical breakthrough in nearly 30 years.

Osteosarcoma (OS) is rare in children, but common in dogs, making “it a prime candidate for the kind of comparative cancer biology studies that could enhance drug development for both children and our canine friends,” says researcher Will Hendricks, Ph.D., an assistant professor in TGen's Integrated Cancer Genomics Division.

OS is an aggressive disease and the most common primary bone tumor in dogs and children. Though a relatively rare cancer in humans with fewer than 1,000 cases each year, OS strikes more than 25,000 dogs annually. The survival time, even with treatment, for most dogs is about one year.

Using multiple molecular-level testing platforms, TGen and Tufts researchers sequenced the genomes of 59 dogs, finding that canine OS shares many of the genomic features of human OS, including lowmutation rates, structural complexity, altered cellular pathways, and unique genetic features of metastatic tumors that spread to other parts of the dog’s body.

The study identified new features of canine OS, including recurrent and potentially cancer-causing mutations in two genes, SETD2 and DMD (the largest known human gene). The study suggests that these findings merit further exploration.

Although surgery and chemotherapy can extend survival, about 30 percent of pediatric OS patients die from metastatic tumors within five years. The cancer moves much faster in dogs, with more than 90 percent succumbing to metastatic disease within two years.

“The genetic similarity between dogs and humans provides a unique opportunity and a comparative model that will enable the development of new therapies within a compressed timeline,” says lead author Heather L. Gardner, DVM, a Ph.D. candidate in Tufts’ Sackler School of Graduate Biomedical Sciences.

Jeffrey Trent, Ph.D., FACMG, TGen President and Research Director, and a contributing author, says the comparative oncology approach is vital to the rapid development of new treatments for people and pets that need help today.

“Leveraging the similarities between the human and canine forms of OS adds greatly to our understanding of how this aggressive cancer develops and spreads. More importantly, it provides an opportunity to develop therapies that make a difference in the lives of children and pets,” said Dr. Trent, a long-time proponent of comparative oncology.

Gardner, HL, et al. Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2.Communications Biology, 2019; 2 (1) DOI:10.1038/s42003-019-0487-2. Science Daily.

This article has been reprinted with permission from Cornell University College of Veterinary Medicine’s DOGWatch Newsletter, published by Belvoir Media Group. Subscribe online to DOGWatch Newsletter here.