Several purebred dogs, like various retrievers, Bernese Mountain Dogs, and Rottweilers, have a high incidence of histiocytic sarcoma (HS) as well as other cancers such as lymphoma or undifferentiated sarcoma. Diagnosing HS can be challenging, particularly without visible masses or proper immunohistochemistry. In fact, misdiagnoses of HS accounts for nearly 20% of reported cases in certain breeds. Unfortunately, there is currently no effective treatment for this devastating cancer, thus impacting the longevity of the predisposed breeds. Late diagnosis and limited understanding of its genetic basis hinder the management of canine HS.

With funding from a previous CHF grant, #02446: Development of Genetic Biomarkers to Improve Diagnosis and Treatment of Canine Histiocytic Sarcoma, the researchers identified recurrent somatic mutations in HS through exome sequencing of 30 tumors, enhancing their knowledge of its genetic basis. By discovering distinct PTPN11 mutations in tumors from the same dogs, they have demonstrated that these mutations are associated with the spread of HS in dogs and humans. In addition, the investigators are able to determine the chronology of mutations in the development of HS. Utilizing these PTPN11 mutations, researchers have developed a blood test that can accurately detect HS an average of 7.3 months before clinical signs appear. The hypothesis is that these and additional, novel somatic mutations can enable a much earlier diagnosis and, consequently, the introduction of more effective treatments. The researchers will test this hypothesis by pursuing two objectives: (1) identifying other and earlier somatic mutations of HS, and (2) determining the feasibility of diagnosing HS before the onset of clinical signs, leading to improved management of this cancer in veterinary and human medicine.