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Humans with\n                    <jats:italic>TP53<\/jats:italic>\n                    germline mutations are predisposed to a wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss of p53 function has been observed in &gt;50% of human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert to a transformed phenotype after activation of latent oncogenic\n                    <jats:italic>TP53<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>R167H<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G12D<\/jats:italic>\n                    <\/jats:sup>\n                    , and overexpression of MYC promotes tumorigenesis. The process mimics key molecular aspects of human sarcomagenesis. Transformed porcine MSCs exhibit genomic instability, with complex karyotypes, and develop into sarcomas on transplantation into immune-deficient mice. In pigs, heterozygous knockout of\n                    <jats:italic>TP53<\/jats:italic>\n                    was sufficient for spontaneous osteosarcoma development in older animals, whereas homozygous\n                    <jats:italic>TP53<\/jats:italic>\n                    knockout resulted in multiple large osteosarcomas in 7\u20138-month-old animals. This is the first report that engineered mutation of an endogenous tumour-suppressor gene leads to invasive cancer in pigs. Unlike in\n                    <jats:italic>Trp53<\/jats:italic>\n                    mutant mice, osteosarcoma developed in the long bones and skull, closely recapitulating the human disease. These animals thus promise a model for juvenile osteosarcoma, a relatively uncommon but devastating disease.\n                  <\/jats:p>","DOI":"10.1038\/oncsis.2016.19","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T10:23:25Z","timestamp":1457951005000},"page":"e210-e210","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["A porcine model of osteosarcoma"],"prefix":"10.1038","volume":"5","author":[{"given":"A","family":"Saalfrank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K-P","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ravon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Flisikowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Eser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Steiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Flisikowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"M\u00fcller-Fliedner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Br\u00f6nner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Gnann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Kappe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"B\u00f6hm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Schade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Certa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Saur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Schnieke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"BFoncsis201619_CR1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ccr.2004.07.009","volume":"6","author":"A Rangarajan","year":"2004","unstructured":"Rangarajan A, Hong SJ, Gifford A, Weinberg RA . 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