Sarcomas of the second type, for example, fibrosarcoma, liposarcoma, chondrosarcoma and osteosarcoma, often have TP53 and RB1 mutations.11, 12 Consistent with this, transformation of human mesenchymal stem cells (MSCs) requires disruption of the p53 and Rb tumour-suppressor pathways, stabilisation of MYC, activation of oncogenic RAS and telomere maintenance.13 We report that targeted mutation of endogenous porcine TP53 and KRAS in primary MSCs results in neoplastic transformation and tumorigenesis. This evidence concerns the gene RB1 and osteosarcoma.