Discovery of Human-Similar Gene Fusions in Canine Cancers

Ronan Ulvé (1) , Mélanie Rault (1) , Mathieu Bahin (1) , Laetitia Lagoutte (1) , Jérôme Abadie (2, 3) , Clotilde de Brito (1) , Jean-Michel Coindre (4) , Nadine Botherel (1) , Audrey Rousseau (5) , Valentin Wucher (1) , Edouard Cadieu (1) , Catherine Thieblemont (6) , Christophe Hitte (7) , Laurence Cornevin (8) , Florian Cabillic (8, 9) , Laura Bachelot (7) , David Gilot (7) , Benoit Hennuy (10) , Thierry Guillaudeux (11, 12, 13, 14) , Arnaud Le Goff (12) , Thomas Derrien (1) , Benoît Hédan (1) , Catherine André (1)

1 IGDR - Institut de Génétique et Développement de Rennes
2 ONIRIS - École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique
3 AMaROC - Animaux modèles pour la recherche en oncologie comparée
4 Service de Pathologie
5 MINT - Micro et Nanomédecines Translationnelles
6 Hôpital Saint-Louis
7 IGDR - Institut de Génétique et Développement de Rennes
8 Service de Cytogénétique et de Biologie Cellulaire
9 NuMeCan - Nutrition, Métabolismes et Cancer
10 Université de Liège
11 MiCa - Microenvironnement et cancer
12 Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes
13 ImPACcell - Plate-forme ImPACcell
14 COSS - Chemistry, Oncogenesis, Stress and Signaling

Canine cancers represent a tremendous natural resource due to their incidence and striking similarities to human cancers, sharing similar clinical and pathologic features as well as oncogenic events, including identical somatic mutations. Considering the importance of gene fusions as driver alterations, we explored their relevance in canine cancers. We focused on three distinct human-comparable canine cancers representing different tissues and embryonic origins. Through RNA-Seq, we discovered similar gene fusions as those found in their human counterparts: IGK-CCND3 in B-cell lymphoma, MPB-BRAF in glioma, and COL3A1-PDGFB in dermatofibrosarcoma protuberans-like. We showed not only similar partner genes but also identical breakpoints leading to oncogene overexpression. This study demonstrates similar gene fusion partners and mechanisms in human-dog corresponding tumors and allows for selection of targeted therapies in preclinical and clinical trials with pet dogs prior to human trials, within the framework of personalized medicine.

Mots clés: Fusions; spontaneous model; cancer; dog

Domaines: Génétique; Cancer

Ronan Ulvé, Mélanie Rault, Mathieu Bahin, Laetitia Lagoutte, Jérôme Abadie, et al.. Discovery of Human-Similar Gene Fusions in Canine Cancers. Cancer Research, 2017, 77 (21), pp.5721-5727. ⟨10.1158/0008-5472.CAN-16-2691⟩. ⟨hal-01647128⟩