A porcine model of osteosarcoma

• DOI: 10.1038/oncsis.2016.19
• Publication Date: 2016-03-14T14:23:25Z
• Authors: A Saalfrank; K-P Janssen; M Ravon; K Flisikowski; S Eser; K Steiger; T Flisikowska; P Müller-Fliedner; É Schulze; C Brönner; A Gnann; E Kappe; B Böhm; B Schade; U Certa; D Saur; I Esposito; A Kind; A Schnieke
• Keywords: 0303 health sciences; 03 medical and health sciences; Original Article; ddc:; 3. Good health

We previously produced pigs with a latent oncogenic TP53 mutation. Humans germline mutations are predisposed to wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss p53 function has been observed in >50% human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert transformed phenotype after activation TP53(R167H) KRAS(G12D), overexpression MYC promotes tumorigenesis. The process mimics key molecular aspects sarcomagenesis. Transformed MSCs exhibit genomic instability, complex karyotypes, develop into on transplantation immune-deficient mice. In pigs, heterozygous knockout was sufficient for spontaneous osteosarcoma development older animals, whereas homozygous resulted multiple large osteosarcomas 7-8-month-old animals. This is the first report engineered mutation an endogenous tumour-suppressor gene leads invasive cancer pigs. Unlike Trp53 mutant mice, developed long bones skull, closely recapitulating disease. These animals thus promise model juvenile osteosarcoma, relatively uncommon but devastating