Study reveals genetic similarities of osteosarcoma between dogs and children

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BOSTON, Mass. AND PHOENIX, Arizona, (July 19, 2019) – A bone tumor known as osteosarcoma is genetically similar in dogs and human children, according to the results of a study published today by Tufts University and by Translational Genomics Research Institute (TGen), a subsidiary of City of hope. The findings could help break the impasse in the treatment of this deadly disease, which has not seen significant medical progress in nearly three decades.

"While osteosarcoma (OS) is rare in children, it is very common in many breeds of dogs, making it a leading candidate for the type of comparative cancer biology studies that could improve drug development for both children for our canine friends, "he said Will Hendricks, Ph.D., Assistant Professor in TGen Integrated Cancer Genomics Division and one of the senior authors of the study.

Using multiple test platforms at the molecular level, TGen and Tufts researchers sequenced the genomes of 59 dogs, discovering that the canine operating system shares many of the genomic features of the human operating system, including low mutation rates, structural complexity, and altered pathways Cells and genetic characteristics unique to metastatic tumors that spread to other parts of the body.

Results of the study appeared today in the journal Nature, Biology of communications.

"These results lay the groundwork for understanding the development of the operating system in dogs and humans and establishing genomic contexts for future comparative analyzes," he said. Cheryl A. London, DVM, Ph.D., Anne Engen and Dusty Professor in Comparative Oncology at Cummings School of Veterinary Medicine at Tufts University, and the other senior author of the study.

The study also identified new features of the canine operating system, including recurrent and potentially carcinogenic mutations in two genes, SETD2 and DMD. The study suggests that these results deserve further study.

OS is an aggressive disease and the primary bone cancer most commonly diagnosed in dogs and children. Although it is a relatively rare cancer in humans – with less than 1,000 cases each year – the OS affects more than 25,000 dogs per year.

Although surgery and chemotherapy may prolong survival, approximately 30% of pediatric OS patients die as a result of metastatic tumors within 5 years. Cancer moves much faster in dogs, with over 90% succumbing to metastatic disease within 2 years.

"The genetic similarity between dogs and humans offers a unique opportunity and a comparative model that will allow the development of new therapies within a compressed timeline," he said. Heather L. Gardner, DVM, a PhD candidate at Tufts' Sackler School of Graduate Biomedical Sciences and lead author of the study.

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

"Exploiting the similarities between human and canine forms of OS greatly adds to our understanding of how this aggressive cancer develops and spreads. More importantly, it offers the opportunity to develop therapies that make a difference in children's lives and pets, "said Dr. Trent, who has been a supporter of comparative oncology for over a decade.

Dana-Farber Cancer Institute, Broad Institute, Ohio State University, Colorado State University and University of Texas also contributed to this study: the genome sequencing of the osteosarcoma dog identifies recurrent mutations in DMD and in the histone methyltransferase SETD2 gene. DOI: https://doi.org/10.1038/s42003-019-0487-2.

Funding for this research was provided by the National Institutes of Health, the National Cancer Institute, the National Center for Advancing Translational Sciences, the Dana-Farber / Harvard Cancer Center and the Ohio Comprehensive Cancer Center of the Ohio State University.

No dogs were harmed during this research. Only tissue samples from pet dogs with naturally occurring cancers were examined.

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