For the first time, scientists have mapped the genetic makeup of a rare and aggressive bone cancer that begins in a dog’s jawbone. Led by Darwin’s Ark affiliate researchers, this study offers new insights into the genetic drivers of a disease that’s exceptionally difficult to treat.
Most previous studies on canine bone cancer have studied tumors in the limbs, where the disease is more common and easier to treat with surgery. However, little research has delved into the rarer bone tumors that grow in delicate areas like the skull, spine, or ribcage. Until now, scientists understood very little about what causes cancer in these areas, or if these tumors have any genetic similarities to bone tumors in the limbs.
By sequencing the DNA of jawbone tumors, researchers identified several genes linked to oral bone tumor development in dogs. Interestingly, some of these genes also show up in more common forms of bone cancer in both dogs and humans, suggesting a possible shared genetic link. These early findings could guide further study into the genetic drivers of bone cancer, and with time, could help researchers develop more effective, targeted therapies for both dogs and people facing this aggressive cancer.
Osteosarcoma’s rarer form presents unique treatment challenges
Bone cancer, or osteosarcoma, is one of the most commonly diagnosed cancers in dogs. Most of the time, osteosarcoma forms in the long bones of the legs. But in about 10 percent of cases, the cancer appears in other parts of the skeleton, such as the spine, skull, or ribcage. This rarer form is called axial osteosarcoma, and it is much more challenging to treat.
It is difficult, if not impossible, to surgically remove bone tumors in the axial skeleton. These tumors grow near vital organs and structures, making surgery risky or infeasible. Patients with inoperable tumors face a higher risk of developing metastatic disease, which is when cancer spreads from the original tumor site to other parts of the body. While chemotherapy can help slow the tumor’s growth, chemotherapy without surgery usually isn’t enough to stop osteosarcoma. As a result, patients with inoperable tumors in the axial skeleton have fewer treatment options and face lower survival rates.
To develop better treatments for dogs with osteosarcoma in the spine, skull, or ribcage, scientists need to understand what causes the cancer at the genetic level. Currently, there are no approved gene therapies for osteosarcoma (for neither dogs nor people). Gene therapy is a type of personalized medicine that modifies a patient’s own genes to address disease-causing genetic mutations. For cancer, gene therapy could look like fixing a faulty gene, inactivating a cancer-causing gene, or inserting a new gene that helps fight the disease.
But before these kinds of lifesaving therapies can be developed, scientists first need to determine which genes are involved in the growth and spread of axial osteosarcoma.
Canine axial and limb osteosarcoma share striking genetic similarities
To explore the genetics of canine oral osteosarcoma—and how it compares to the more common limb-based osteosarcoma—a team of researchers led by Darwin’s Ark scientists conducted a small pilot study. They analyzed samples from eight dogs with oral osteosarcoma, and compared tumor samples with healthy bone tissue samples from the same animals. Their goal was to identify genetic changes linked to oral bone tumors and whether they match genetic changes found in limb-based osteosarcoma.
The study’s results were promising: oral and limb-based osteosarcoma share many of the same genetic features. This suggests that, despite forming in different parts of the body, these cancers may develop in similar ways and may respond to similar treatments.
The researchers found that a significant portion of the study’s tumor samples had disruptions in biological pathways that control cell growth. Uncontrollable cell growth is a hallmark of cancer. For inoperable tumors—like many axial osteosarcomas—this kind of unchecked growth is especially dangerous because it’s easier for the cancer to spread to other parts of the body. For these cases, it’s especially important to develop treatments that target genes and pathways that fuel uncontrolled cell growth so that the cancer’s growth can be slowed or stopped before it spreads.
One gene that’s affected in both oral and limb-based osteosarcoma is SETD2, which helps regulate cell growth, division, and repair. Previous studies have found SETD2 mutated in canine osteosarcomas in the limbs, as well as in human cancers that often have poor responses to chemotherapy. Its mutation in dogs with oral osteosarcoma suggests it may play a similar role across species, and could be a target for future treatments in both dogs and people.
Laying the groundwork for future discoveries
This pilot study’s findings lay important foundations for future research. Small exploratory studies like this are often the first step toward more detailed investigations with larger sample sizes. This pilot study identified several key genes and pathways involved in dog bone cancer that are worth studying further.
Notably, every tumor sample in the study had extra copies of at least one of three genes—ZFHX3, KCNQ3, and MYC—that control cell growth and communication. Extra copies of these genes can fuel tumor growth and make cancer cells more resistant to chemotherapy.
Several of the study’s tumor samples also had genetic abnormalities in a biological pathway that helps brain cells communicate. Mutations to genes in this pathway, called the neurexin and neuroligin pathway, have also been linked to limb-based osteosarcoma. The fact that it appears in both forms of osteosarcoma makes it an intriguing target for further investigation, because developing therapies that target shared genetic features could help dogs with either type of osteosarcoma.
Finally, the researchers noted several genetic similarities between canine osteosarcoma and human osteosarcoma. While osteosarcoma is ten times more prevalent in dogs than in humans, it’s the most common type of bone cancer in children and teens. Osteosarcoma behaves similarly in dogs and humans, including its severity and the types of bones it affects. These genetic similarities across species mean that studying osteosarcoma in dogs can also benefit human medicine. Studying genetic features common to both canine and human tumors can help researchers identify targets for therapies that could help both dogs and people facing this aggressive disease.
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Resources
- Husted C, Adrianowycz S, Megquier K, Gardner HL, et al. (2025) Characterization of the genomic landscape of canine oral osteosarcoma reveals similarities with appendicular osteosarcoma. PLoS One 20(6): e0325181. https://doi.org/10.1371/journal.pone.0325181
- Gardner, H.L., Sivaprakasam, K., Briones, N. et al. Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2. Commun Biol 2, 266 (2019). https://doi.org/10.1038/s42003-019-0487-2
- Megquier K, Turner-Maier J, Morrill K, Li X, Johnson J, Karlsson EK, et al. (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
