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Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma

Anaïs Prouteau, Jérôme Alexandre Denis, Pauline De Fornel, Edouard Cadieu, Thomas Derrien, Camille Kergal, Nadine Botherel, Ronan Ulvé, Mélanie Rault, Amira Bouzidi, Romain François, Laetitia Dorso, Alexandra Lespagnol, Patrick Devauchelle, Jérôme Abadie, Catherine André, Benoît Hédan
doi: https://doi.org/10.1101/2020.07.10.189118
Anaïs Prouteau
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Jérôme Alexandre Denis
2Sorbonne University, INSERM UMR_S938, APHP Pitié-Salpêtrière Hospital, Endocrinology and oncology Biochemistry department, Paris, France
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Pauline De Fornel
3Micen Vet, Créteil, France
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Edouard Cadieu
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Thomas Derrien
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Camille Kergal
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Nadine Botherel
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Ronan Ulvé
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Mélanie Rault
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Amira Bouzidi
2Sorbonne University, INSERM UMR_S938, APHP Pitié-Salpêtrière Hospital, Endocrinology and oncology Biochemistry department, Paris, France
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Romain François
3Micen Vet, Créteil, France
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Laetitia Dorso
4Oniris, Laboniris - Department of Biology, Pathology and Food Sciences, Nantes, France
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Alexandra Lespagnol
5Laboratory of somatic genetic of cancers, Hospital of Rennes, France
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Patrick Devauchelle
2Sorbonne University, INSERM UMR_S938, APHP Pitié-Salpêtrière Hospital, Endocrinology and oncology Biochemistry department, Paris, France
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Jérôme Abadie
4Oniris, Laboniris - Department of Biology, Pathology and Food Sciences, Nantes, France
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Catherine André
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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Benoît Hédan
1CNRS-University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
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  • For correspondence: benoit.hedan@univ-rennes1.fr
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Abstract

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology and may be informative in cancer-affected dogs. By performing ddPCR or PARR methods, we detected tumor-specific point mutations, copy number alterations and chromosomal rearrangements in the plasma of cancer-affected dogs. It allowed the detection of ctDNA in 2/8 (25%) oral malignant melanoma cases, 12/13 (92.3%) lymphoma cases and 21/23 (91.3%) histiocytic sarcoma (HS) cases. The value of ctDNA to diagnose HS was explored in 133 dogs including 49 with HS. In this cohort, screening recurrent PTPN11 mutations in plasma had a specificity of 98.8%, and a sensitivity between 42.8-77% according to HS clinical presentation, being higher in internal forms, especially with pulmonary location. Regarding lymphoma, the follow-up of four dogs showed that the minimal residual disease detection by targeting lymphoma-specific antigen receptor rearrangement in the plasma was concordant with the clinical evaluation. Moreover, ctDNA analysis appeared interesting to assess treatment response and to predict relapse.

This study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a relevant biomarker for diagnosis and clinical follow-up. With a growing interest in integrating natural canine tumors to explore new therapies, this biomarker appears promising in comparative oncology research.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 11, 2020.
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Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma
Anaïs Prouteau, Jérôme Alexandre Denis, Pauline De Fornel, Edouard Cadieu, Thomas Derrien, Camille Kergal, Nadine Botherel, Ronan Ulvé, Mélanie Rault, Amira Bouzidi, Romain François, Laetitia Dorso, Alexandra Lespagnol, Patrick Devauchelle, Jérôme Abadie, Catherine André, Benoît Hédan
bioRxiv 2020.07.10.189118; doi: https://doi.org/10.1101/2020.07.10.189118
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Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma
Anaïs Prouteau, Jérôme Alexandre Denis, Pauline De Fornel, Edouard Cadieu, Thomas Derrien, Camille Kergal, Nadine Botherel, Ronan Ulvé, Mélanie Rault, Amira Bouzidi, Romain François, Laetitia Dorso, Alexandra Lespagnol, Patrick Devauchelle, Jérôme Abadie, Catherine André, Benoît Hédan
bioRxiv 2020.07.10.189118; doi: https://doi.org/10.1101/2020.07.10.189118

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