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MPM harbors loss\u2010of\u2010function mutations in\n                    <jats:italic>BAP1<\/jats:italic>\n                    ,\n                    <jats:italic>NF2<\/jats:italic>\n                    ,\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    , and\n                    <jats:italic>TP53<\/jats:italic>\n                    , but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of\n                    <jats:italic>KRAS<\/jats:italic>\n                    with or without\n                    <jats:italic>TP53<\/jats:italic>\n                    changes. These are likely pathogenic, since ectopic expression of mutant\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with\n                    <jats:italic>TP53<\/jats:italic>\n                    deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    lesions, secondary\n                    <jats:italic>Bap1<\/jats:italic>\n                    alterations, and human MPM\u2010like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that\n                    <jats:italic>KRAS<\/jats:italic>\n                    alterations alone or in accomplice with\n                    <jats:italic>TP53<\/jats:italic>\n                    alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202013631","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T03:08:07Z","timestamp":1639364887000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["KRAS signaling in malignant pleural mesothelioma"],"prefix":"10.1038","volume":"14","author":[{"given":"Antonia","family":"Marazioti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthi 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