In the physiological state, the cells of our body release DNA into our bloodstream via necrosis, apoptosis or secretion phenomena. This DNA, which is found in plasma and other biological fluids, is called circulating DNA and its concentration increases in various pathological processes such as inflammation, sepsis, stroke and cancer. In cancer patients, some of the circulating DNA comes from the tumor cells and is thus called circulating tumor DNA (ctDNA). This ctDNA is characterized by the presence of tumor genetic and epi-genetic alterations that are advantageous for cancer development and progression, as well as for resistance to certain therapies.
In human oncology, the detection and analysis of tcDNA has become possible thanks to recent sequencing and digital PCR techniques, allowing many applications from a simple blood sample, in a non-invasive way. The main promising applications for this biomarker are:
- early diagnosis of cancer
- after diagnosis, to characterize a tumor more precisely in order to determine the prognosis of the disease and make appropriate therapeutic choices
- during treatment, to monitor the effectiveness of the treatments: if the circulating tumor DNA is less abundant, it means that the tumor is regressing.
For the past few years, our CNRS "Dog Genetics" team has been working on the development of tcDNA analysis tests in canine oncology, particularly in two cancers: histiocytic sarcoma (HS) and lymphoma.
Histiocytic sarcoma (HS) is a very aggressive form of cancer of macrophagic cells. Although it can be diagnosed in several breeds, a few breeds are highly susceptible: the Bernese Mountain Dog, the Rottweiler and the Retriever. The Dog Genetics team has been working for more than 15 years on the genetic basis of this cancer, in order to better understand the development of this cancer and to improve its management. The team has identified mutations that are shared between canine and human histiocytic sarcomas. These mutations are present in half (56%) of canine histiocytic tumors (Hedan et al. 2020). These tumor-specific mutations are also detectable in the plasma of diseased dogs and can be used to diagnose the presence of a histiocytic sarcoma. Thus with a simple blood and plasma sample, we have shown that it is possible to diagnose histiocytic sarcoma with a sensitivity of 42.8% and a specificity of 98.8%. Thus, our non-invasive plasma test proves to be of interest when there is a suspicion of histiocytic sarcoma in dogs, particularly in the presence of internal masses.
For lymphoma, we showed that tcDNA was detected in 92.3% of cases at diagnosis. The follow-up of this biomarker in 4 dogs with diffuse large cell B lymphoma receiving chemotherapy showed a very good correlation with the response to treatment, and in one case, a molecular relapse was observed 42 days before the clinical relapse. This plasma test is interesting for monitoring residual disease in dogs undergoing chemotherapy treatment, to evaluate the response to treatment and to anticipate relapse.
Prouteau A, Denis JA, 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. Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma. Sci Rep. 2021 Jan 13;11(1):877. doi: 10.1038/s41598-020-80332-y. PMID: 33441840 F
Team: Dog Genetics, IGDR.