Osteosarcoma occurs spontaneously in humans (usually children) and in dogs with a disease course and severity that are difficult to predict. Some patients respond well to conventional therapies, have a less aggressive form of disease and may survive for decades without recurrence, whereas others respond poorly to treatment or experience recurrence and may survive less than 5 years. This variability has hindered accurate molecular classification of osteosarcomas.

Because spontaneous osteosarcoma occurs more frequently in certain breeds of dogs than in others, researchers hypothesized that it would be easier to identify molecular subtypes of osteosarcoma on the more genetically homogeneous canine background. They also believed that these molecular profiles could be used to similarly identify clinically relevant subtypes in human samples in order to better predict therapeutic success. The group, led by Jaime F. Modiano (University of Minnesota, Minneapolis), carried out extensive genetic analyses of tumor cell and whole tumor samples from dogs with osteosarcomas. They were able to group the tumors into two distinct branches (A and B) on the basis of differences in expression of two clusters of genes (Bone 49, 356–367; 2011).

Samples from independent data sets showed the same grouping and expression differences, indicating that the molecular signatures were robust across canine osteosarcomas. Next, the researchers assessed several sets of human osteosarcoma samples to determine whether the same molecular signatures were present. They observed clustering patterns similar to those identified in canines.

Having established that two subtypes of osteosarcoma could be identified in both dogs and humans, they next evaluated the clinical relevance of the two subtypes. Overall survival among dogs with branch A tumors was significantly lower than among those with branch B tumors. Time to metastasis was also shorter for dogs with branch A versus branch B tumors. In humans, branch B tumors were generally associated with better clinical outcome than branch A tumors.

“Our findings pave the way to develop laboratory tests that can predict the behavior of this tumor in dogs and children at the time of diagnosis,” said Modiano in a press release. “This allows us to tailor individualized therapy to meet the patient's needs... patients with less aggressive disease could be treated conservatively, reducing the side effects and the risks associated with treatment, while patients with more aggressive disease could be treated with more intense therapy.”