Introduction
If you own a Bernese Mountain Dog, Flat-Coated Retriever, or another large breed, this breakthrough could be life-changing. A devastating cancer called histiocytic malignancy (HM) is striking these dogs at alarming rates, and researchers are finally uncovering why.
Thanks to cutting-edge genetic research funded by the AKC Canine Health Foundation, scientists are identifying the unique genetic markers of HM. These discoveries could lead to faster, more accurate diagnoses and better treatment options for affected dogs.
Key Points
- HM accounts for up to 64% of all cancers in Bernese Mountain Dogs and 60% of splenic tumors in Flat-Coated Retrievers.
- Clinical signs are vague—fever, weight loss, lethargy, and visible masses—making early diagnosis difficult.
- Researchers found unique genetic changes in HM that distinguish it from other cancers like lymphoma and hemangiosarcoma.
- A blood test is in development to diagnose HM earlier and guide targeted treatment.
- HM shows extensive chromosomal variation, which may explain poor response to current treatments.
The Impact of Canine Histiocytic Malignancies
Histiocytic malignancies are rare but aggressive cancers that disproportionately affect certain breeds, especially Bernese Mountain Dogs and Flat-Coated Retrievers. These cancers often go undetected until they’ve spread to multiple organs, making treatment difficult and survival rates low.
Before this research, veterinarians struggled to distinguish HM from other cancers with similar symptoms, like lymphoma. This led to delays in diagnosis and mismatched treatments, worsening outcomes for affected dogs.
Tracing Research Advancements
Researchers at North Carolina State University, supported by CHF, conducted genome-wide studies to uncover the genetic basis of HM (Grant 01557: Narrowing the Search for the Genetic Basis of Histiocytic Malignancies). Their findings include:
- Extensive copy number alterations on two canine chromosomes. Copy number alterations are a type of structural variation in the genome caused by duplications or deletions and result in an abnormal number of one or more genes. The genetic alterations found in canine HM are deletions of tumor suppressor genes, resulting in more tumors.
- Increased expression of matrix metallopeptidase 9 (MMP-9) gene and protein levels. MMP-9 is involved in tumor progression and metastasis in human cancer and may contribute to the aggressive nature of HM in dogs.
- Wide variation in the number of chromosomes present in cells from the same and different tumors. Such variety may explain why treatment response is so poor – any one treatment may not eliminate 100% of the cancerous cells.
These genetic markers are unique to HM, allowing scientists to differentiate it from other cancers with high accuracy. This paves the way for a rapid diagnostic test and more personalized treatment strategies.
Driving Progress Today
The next step is developing a blood test to detect HM early and guide treatment decisions. This work, funded by CHF and led by researchers at the University of Rennes in France, could dramatically improve survival rates (Grant 02446: Development of Genetic Biomarkers to Improve Diagnosis and Treatment of Canine Histiocytic Sarcoma).
Beyond diagnostics, understanding HM’s genetic profile may lead to targeted therapies that are more effective than current options. Researchers also hope to collaborate with human oncology experts, as HM shares similarities with rare human sarcomas, potentially benefiting both dogs and people.
Support canine cancer research at akcchf.org/cancer.
References:
Kennedy, K., Thomas, R., & Breen, M. (2016). Canine Histiocytic Malignancies—Challenges and Opportunities. Veterinary Sciences, 3(1), 2. https://doi.org/10.3390/vetsci3010002
Kennedy, K., Thomas, R., Durrant, J., Jiang, T., Motsinger-Reif, A., & Breen, M. (2019). Genome-wide DNA copy number analysis and targeted transcriptional analysis of canine histiocytic malignancies identifies diagnostic signatures and highlights disruption of spindle assembly complex. Chromosome Research. https://doi.org/10.1007/s10577-019-09606-0
