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A significant proportion of <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content> patients may also develop myeloproliferative disorders (<jats:styled-content style=\"fixed-case\">MPDs<\/jats:styled-content>), including juvenile myelomonocytic leukaemia (<jats:styled-content style=\"fixed-case\">JMML<\/jats:styled-content>). Surprisingly, scarce information is available in relation to other tumour types in these patients. We have previously developed and characterized a knock\u2010in mouse model that carries one of the most frequent <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\u2010related mutations, the K<jats:italic>\u2010Ras<\/jats:italic><jats:sup>V14I<\/jats:sup> substitution, which recapitulates most of the alterations described in NS patients, including MPDs. The K<jats:italic>\u2010Ras<\/jats:italic><jats:sup>V14I<\/jats:sup> mutation is a mild activating K\u2010Ras protein; thus, we have used this model to study tumour susceptibility in comparison with mice expressing the classical K\u2010<jats:italic>Ras<\/jats:italic><jats:sup>G12V<\/jats:sup> oncogene. Interestingly, our studies have shown that these mice display a generalized tumour predisposition and not just MPDs. In fact, we have observed that the K<jats:italic>\u2010Ras<\/jats:italic><jats:sup>V14I<\/jats:sup> mutation is capable of cooperating with the <jats:italic>p16Ink4a\/p19Arf<\/jats:italic> and <jats:italic>Trp53<\/jats:italic> tumour suppressors, as well as with other risk factors such as pancreatitis, thereby leading to a higher cancer incidence. In conclusion, our results illustrate that the K\u2010<jats:styled-content style=\"fixed-case\">Ras<jats:sup>V14I<\/jats:sup><\/jats:styled-content> activating protein is able to induce cancer, although at a much lower level than the classical K\u2010<jats:italic>Ras<\/jats:italic><jats:sup>G12V<\/jats:sup> oncogene, and that it can be significantly modulated by both genetic and non\u2010genetic events. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4719","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T09:05:33Z","timestamp":1458637533000},"page":"206-217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["K\u2010<scp>Ras<sup>V14I<\/sup><\/scp>\u2010induced Noonan syndrome predisposes to tumour development in mice"],"prefix":"10.1002","volume":"239","author":[{"given":"Isabel","family":"Hern\u00e1ndez\u2010Porras","sequence":"first","affiliation":[{"name":"Molecular Oncology Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J","family":"Schuhmacher","sequence":"additional","affiliation":[{"name":"Molecular Oncology Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO)  Madrid 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