Discovery of Human-Similar Gene Fusions in Canine Cancers

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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

Edité par CCSD ; American Association for Cancer Research -

International audience. 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.

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