Introduction

In the recent years, circulating tumor DNA (ctDNA) analysis has become an attractive noninvasive technique to monitor human cancer patients, opening a variety of clinical applications.

Aim of This Study

1) To look for the presence of ctDNA in the plasma of dogs with histiocytic sarcoma, oral melanoma and lymphoma. 2) To assess whether ctDNA can be used to monitor minimal residual disease in dogs with high-grade lymphoma treated by chemotherapy.

Methods

We collected tumor and plasma samples from 21 dogs with histiocytic sarcoma, 10 with oral melanoma and 14 with high-grade multicentric lymphoma comprising 4 dogs treated by chemotherapy. ctDNA was identified by detecting specific recurrent somatic alterations (point mutation, copy number alteration (CNA) or chromosomal rearrangement) with digital droplets PCR (ddPCR), and PCR for antigen receptor rearrangement (PARR).

Results

For histiocytic sarcomas, the targeted mutation was detected in 9/21 tumors and ctDNA was detected in all of the 9 corresponding plasmas. Concerning oral melanoma, CNA were identified in 9/10 tumors and one dog had the corresponding CNA detectable in its plasma. About dogs with lymphoma, the PARR assay was positive for 13/14 tumors, and ctDNA was detected in the plasma of 12/13 dogs at time of diagnosis. Four dogs with lymphoma received chemotherapy and minimal residual disease (MRD) was determined before each chemotherapy injection, by targeting lymphoma-specific antigen receptor rearrangement in their plasma. The detection of MRD was concordant with the evaluation of the clinical response and ctDNA analysis appears highly sensitive to assess treatment response.

Conclusions

This study shows that ctDNA is detectable in the plasma of dogs with various cancers, especially in HS and lymphoma (100% of HS and 92% of dogs with lymphoma) and is a promising biomarker for diagnosis and clinical follow-up in veterinary oncology.