Discovery of Human-Similar Gene Fusions in Canine Cancers

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 21; pp. 5721 - 5727
• Main Authors: Ulvé, Ronan, Rault, Mélanie, Bahin, Mathieu, Lagoutte, Laetitia, Abadie, Jérôme, De Brito, Clotilde, Coindre, Jean-Michel, Botherel, Nadine, Rousseau, Audrey, Wucher, Valentin, Cadieu, Edouard, Thieblemont, Catherine, Hitte, Christophe, Cornevin, Laurence, Cabillic, Florian, Bachelot, Laura, Gilot, David, Hennuy, Benoit, Guillaudeux, Thierry, Le Goff, Arnaud, Derrien, Thomas, Hédan, Benoît, André, Catherine
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 01.11.2017; American Association for Cancer Research
• Subjects: Animals; B-cell lymphoma; Base Sequence; Blotting, Western; Brain tumors; Breakpoints; Cancer; Chromosome Breakpoints; Clinical trials; Dermatofibrosarcoma protuberans; Dog Diseases - genetics; Dog Diseases - metabolism; Dogs; Embryos; Gene Expression Regulation, Neoplastic; Gene fusion; Genetics; Glioma - genetics; Glioma - metabolism; Glioma - veterinary; Glioma cells; Humans; Life Sciences; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - metabolism; Lymphoma, B-Cell - veterinary; Mutation; Natural resources; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - veterinary; Oncogene Fusion; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Pets; Precision medicine; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; Tissues; Translocation, Genetic; Tumors; cancer; spontaneous model; dog; Fusions
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-16-2691

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: - in B-cell lymphoma, - in glioma, and - 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. .