Univ. Rennes 1, CNRS, Institut de Geéneétique et de Deéveloppement de Rennes (IGDR), UMR6290, Rennes, France.
BIOTRIAL Pharmacology, Unité de Pharmacologie Preéclinique, Rennes, France.
Cancer Res. 2017 Nov 1;77(21):5721-5727. doi: 10.1158/0008-5472.CAN-16-2691. Epub 2017 Sep 7.
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. .
犬类癌症是一个巨大的天然资源，因为它们的发病率和与人类癌症的惊人相似性，具有相似的临床和病理特征以及致癌事件，包括相同的体细胞突变。考虑到基因融合作为驱动改变的重要性，我们探讨了它们在犬类癌症中的相关性。我们专注于三种不同的具有人类可比性的犬类癌症，代表不同的组织和胚胎起源。通过 RNA-Seq，我们发现了与人类癌症中相似的基因融合：- 在 B 细胞淋巴瘤中，- 在神经胶质瘤中，- 在隆突性皮肤纤维肉瘤样中。我们不仅显示了相似的伙伴基因，而且还显示了导致致癌基因过表达的相同断点。这项研究表明，在人类临床试验之前，在个性化医疗框架内，在临床前和临床试验中使用宠物犬选择靶向治疗是合理的。
