Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma

Anaïs Prouteau,Amira Bouzidi,Romain François,Benoît Hédan,Edouard Cadieu,Thomas Derrien,Pauline De Fornel,Patrick Devauchelle,Mélanie Rault,Catherine André,Nadine Botherel,Camille Kergal,Ronan Ulvé,Laetitia Dorso,Alexandra Lespagnol,Jérôme Abadie,Jérôme Alexandre Denis

doi:10.1038/s41598-020-80332-y

Abstract

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

Highlights

Circulating tumor DNA has become an attractive biomarker in human oncology, and its use may be informative in canine cancer
Plasma samples were collected from 49 dogs with histiocytic sarcoma (17 disseminated forms, 30 localized forms, and 2 unknown), 16 dogs with oral melanoma (OMM), and 25 dogs with multicentric lymphoma (Supplementary Table 1)
Discussion Cell-free DNA (cfDNA) is an attractive biomarker for use in human medicine, in oncology, and it has been evaluated in different canine diseases[16,17,19,20,41,42,43,44]

Summary

Introduction

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. We used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. Our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. CtDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies. The detection of cancer-specific recurrent somatic alterations in plasma may allow the development of novel minimally invasive biomarkers for the diagnosis, prognosis, and assessment of responses to treatment in veterinary medicine. Naturally occurring canine cancers have become relevant models for the study of rare human cancers, and have been used for the discovery of mutations for the development and screening of targeted therapies[27]

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