{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T08:15:12Z","timestamp":1794384912903,"version":"4.9.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,5,27]]},"abstract":"<jats:p>\n                    Oncogenic Kit mutations are found in somatic gastrointestinal (GI) stromal  tumors (GISTs) and mastocytosis. A mouse model for the study of constitutive  activation of Kit in oncogenesis has been produced by a knock-in strategy  introducing a Kit exon 11-activating mutation into the mouse genome based on a  mutation found in a case of human familial GIST syndrome. Heterozygous mutant\n                    <jats:italic>Kit<\/jats:italic>\n                    <jats:sup>V558<\/jats:sup>\n                    <jats:sup>\u0394<\/jats:sup>\n                    \/+ mice develop symptoms of  disease and eventually die from pathology in the GI tract. Patchy hyperplasia  of Kit-positive cells is evident within the myenteric plexus of the entire GI  tract. Neoplastic lesions indistinguishable from human GISTs were observed in  the cecum of the mutant mice with high penetrance. In addition, mast cell  numbers in the dorsal skin were increased. Therefore\n                    <jats:italic>Kit<\/jats:italic>\n                    <jats:sup>V558<\/jats:sup>\n                    <jats:sup>\u0394<\/jats:sup>\n                    \/+ mice reproduce human familial  GISTs, and they may be used as a model for the study of the role and  mechanisms of Kit in neoplasia. Importantly, these results demonstrate that  constitutive Kit signaling is critical and sufficient for induction of GIST  and hyperplasia of interstitial cells of Cajal.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1037763100","type":"journal-article","created":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T13:10:32Z","timestamp":1054041032000},"page":"6706-6711","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":212,"title":["Gastrointestinal stromal tumors in a mouse model by targeted mutation of  the Kit receptor tyrosine kinase"],"prefix":"10.1073","volume":"100","author":[{"given":"Gunhild","family":"Sommer","sequence":"first","affiliation":[{"name":"Developmental Biology and Cell Biology Programs, Molecular Cytology Core Facility, Sloan-Kettering Institute, and Pathology Department, Memorial Sloan-Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences, New York, NY  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