Liquid Biopsy for Canine Histiocytic Sarcoma and Lymphoma
A liquid biopsy is a blood test looking for tumor cells or pieces of tumor DNA that are circulating in the blood stream. There are always small pieces of DNA circulating in bodily fluids after they are released during normal cell death. This circulating DNA usually comes from blood-related tissues such as the bone marrow, spleen, or liver. However, in cancer patients some of this DNA originates from their tumor and is known as circulating tumor DNA (ctDNA). ctDNA is relatively easy to collect through a blood sample and it contains tumor-related genetic and epigenetic characteristics that provide hints about the methods various tumors use to develop, spread, and resist treatment. ctDNA tests are already approved for the detection of non-small-cell lung cancer and colorectal cancer in humans. With funding from AKC Canine Health Foundation (CHF) Grant 02446: Development of Genetic Biomarkers to Improve Diagnosis and Treatment of Canine Histiocytic Sarcoma, investigators at the University of Rennes are studying the use of ctDNA in dogs.
Histiocytic sarcoma is an aggressive cancer of one type of white blood cell in dogs. It can be localized or spread through multiple organ systems. Bernese Mountain Dogs and Flat-Coated Retrievers are breeds at increased risk. Humans can also be affected by this type of cancer, but it is rare, making study in our species a challenge. Histiocytic sarcoma in dogs is a great example of a cancer for which liquid biopsy would be extremely helpful. The disease occurs in the bloodstream and/or internal organs, so there is no visible tumor to biopsy. The clinical signs of histiocytic sarcoma can be nonspecific and resemble those seen with other cancers such as lymphoma and hemangiosarcoma. Because each of these cancers requires a unique treatment strategy and because the prognosis differs greatly, an accurate liquid biopsy would allow earlier diagnosis and more effective treatment.
CHF-funded investigators recently published results of their study on ctDNA in Scientific Reports.1 They found that the total amount of circulating DNA in canine plasma was not a sensitive test for cancer. However, when they tested for circulating DNA containing specific abnormalities associated with different cancers, they had good results.
91% of dogs whose histiocytic sarcoma tumor was positive for a PTPN11 point mutation had a positive ctDNA plasma test. Unfortunately, only about half of canine histiocytic sarcoma tumors contain this mutation. So, the liquid biopsy will not detect all cases of histiocytic sarcoma, but it is very specific for this cancer.
92% of dogs with multicentric lymphoma tested positive for ctDNA containing chromosome abnormalities specific to this cancer.
Investigators also tested for ctDNA with a genetic abnormality specific to oral malignant melanoma, but liquid biopsy was not very accurate for this type of cancer.
In addition to early and non-invasive diagnosis, liquid biopsy may help monitor response to treatment. Investigators found that ctDNA levels in canine lymphoma correlated with each dog’s clinical response. That is, as the cancer cells were killed by treatment, there was less ctDNA measured in the bloodstream.
These results demonstrate that liquid biopsy through measurement of circulating tumor DNA in a blood sample shows promise in diagnosing canine cancers such as histiocytic sarcoma and multicentric lymphoma. It may also provide a tool to monitor treatment response and predict cancer relapse. The AKC Canine Health Foundation and its donors will continue to invest in studies like this using the latest knowledge and technologies to advance the health of dogs and their owners. Learn more about CHF’s oncology research at akcchf.org/oncologyRPA.
1. Prouteau, A., Denis, J. A., De Fornel, P., Cadieu, E., Derrien, T., Kergal, C., Botherel, N., Ulvé, R., Rault, M., Bouzidi, A., François, R., Dorso, L., Lespagnol, A., Devauchelle, P., Abadie, J., André, C., & Hédan, B. (2021). Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma. Scientific Reports, 11(1), 877. https://doi.org/10.1038/s41598-020-80332-y
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