Investigators from the Tufts University and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, have just uncovered that a rare bone cancer in children—known as osteosarcoma (OS)— is genetically similar in dogs. The researchers are optimistic that the findings could help break the logjam in the treatment of this deadly disease, which hasn’t seen a significant medical breakthrough in nearly three decades.
Findings from the new study were published recently in Communications Biology through an article titled “Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2.”
“While OS is rare in children, it is all too common in many dog breeds, which makes it a prime candidate for the kind of comparative cancer biology studies that could enhance drug development for both children and our canine friends,” explained senior study investigator Will Hendricks, Ph.D., an assistant professor in TGen’s Integrated Cancer Genomics Division.
The researchers used multiple molecular-level testing platforms to sequence the genomes of 59 dogs, finding that canine OS shares many of the genomic features of human OS, including low mutation rates, structural complexity, altered cellular pathways, and unique genetic features of metastatic tumors that spread to other parts of the body.
“To define the genomic underpinnings of canine OS, we performed multi-platform analysis of OS tumors from 59 dogs, including whole-genome sequencing (n = 24) and whole exome sequencing (WES; n = 13) of primary tumors and matched normal tissue, WES (n = 10) of matched primary/metastatic/normal samples and RNA sequencing (n = 54) of primary tumors,” the authors wrote. “We found that canine OS recapitulates features of human OS including low point mutation burden (median 1.98 per Mb) with a trend towards higher burden in metastases, high structural complexity, frequent TP53 (71%), PI3K pathway (37%), and MAPK pathway mutations (17%), and low expression of immune-associated genes. We also identified novel features of canine OS including putatively inactivating somatic SETD2 (42%) and DMD (50%) aberrations.”
“These findings set the stage for understanding OS development in dogs and humans, and establish genomic contexts for future comparative analyses,” added co-senior study investigator Cheryl London, DVM, PhD, a professor in comparative oncology at the Cummings School of Veterinary Medicine within Tufts University.
OS is an aggressive disease and the most commonly diagnosed 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.
Although surgery and chemotherapy can extend survival, about 30% of pediatric OS patients die from metastatic tumors within five years. The cancer moves much faster in dogs, with more than 90% 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,” remarked lead study investigator Heather Gardner, DVM, a PhD candidate in Tufts’ Sackler School of Graduate Biomedical Sciences.
The authors were excited by their findings and noted that 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,” concluded study co-author Jeffrey Trent, PhD, TGen president and research director who has been a proponent of comparative oncology for more than a decade.