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We show that the\n                    <jats:italic>TP53<\/jats:italic>\n                    tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of\n                    <jats:italic>Vhl<\/jats:italic>\n                    and\n                    <jats:italic>Trp53<\/jats:italic>\n                    in primary mouse embryo fibroblasts causes proliferative dysregulation and high rates of aneuploidy. Deletion of these genes in the epithelium of the kidney induces the formation of simple cysts, atypical cysts and neoplasms, and deletion in the epithelia of the genital urinary tract leads to dysplasia and tumour formation. Kidney cysts display a reduced frequency of primary cilia and atypical cysts and neoplasms exhibit a pro\u2010proliferative signature including activation of mTORC1 and high expression of Myc, mimicking several cellular and molecular alterations seen in human ccRCC and its precursor lesions. As the majority of ccRCC is associated with functional inactivation of\n                    <jats:italic>VHL<\/jats:italic>\n                    , our findings suggest that for a subset of ccRCC, loss of p53 function represents a critical event in tumour development.\n                  <\/jats:p>","DOI":"10.1002\/emmm.201202231","type":"journal-article","created":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T03:36:56Z","timestamp":1366601816000},"page":"949-964","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice"],"prefix":"10.1038","volume":"5","author":[{"given":"Joachim","family":"Albers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Rajski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9e","family":"Sch\u00f6nenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Harlander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schraml","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"von Teichman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Strahil","family":"Georgiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Wild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Moch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Krek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Frew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,4,22]]},"reference":[{"key":"BFEMMM201202231_CR1","doi-asserted-by":"crossref","first-page":"14391","DOI":"10.1073\/pnas.0907357106","volume":"106","author":"JA Bertout","year":"2009","unstructured":"Bertout JA, Majmundar AJ, Gordan JD, Lam JC, Ditsworth D, Keith B, Brown EJ, Nathanson KL, Simon MC (2009) HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses. 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