{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:17:04Z","timestamp":1758122224703},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,3,19]],"date-time":"2007-03-19T00:00:00Z","timestamp":1174262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2007,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Germline <jats:italic>RET<\/jats:italic> mutations are responsible for different inherited disorders: Hirschsprung disease (congenital aganglionic megacolon), caused by loss of function mutations, familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2, caused by gain of function mutations. Intriguingly, some <jats:italic>RET<\/jats:italic> mutations, including C620R, are associated with both types of diseases. To investigate the dual role of such <jats:italic>RET<\/jats:italic> mutations, a mouse model with a targeted mutation <jats:italic>ret<jats:sup>C620R<\/jats:sup><\/jats:italic> was generated. <jats:italic>ret<jats:sup>C620R\/C620R<\/jats:sup><\/jats:italic> offspring die during the first postnatal day, and show kidney agenesis and intestinal aganglionosis. Decreased outgrowth of the Ret\u2010positive cells was observed in <jats:italic>ret<jats:sup>C620R\/C620R<\/jats:sup><\/jats:italic> neuronal cell cultures, which is suggestive of an impaired migration, proliferation or survival of the Ret\u2010expressing cells. Electronmicroscopy revealed the absence of membrane\u2010bound Ret in <jats:italic>ret<jats:sup>C620R\/C620R<\/jats:sup><\/jats:italic> cells as compared to <jats:italic>ret<jats:sup>+\/+<\/jats:sup><\/jats:italic> and <jats:italic>ret<jats:sup>+\/C620R<\/jats:sup><\/jats:italic> cells. On the other hand, aged <jats:italic>ret<jats:sup>+\/C620R<\/jats:sup><\/jats:italic> mice develop precancerous lesions in the adrenal gland or in the thyroid. Our results suggest that the <jats:italic>ret<jats:sup>C620R<\/jats:sup><\/jats:italic> mutation has a loss of function effect in homozygotes and exhibits a dominant gain of function effect with low penetrance causing hyperplasia in heterozygotes. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.22378","type":"journal-article","created":{"date-parts":[[2007,3,19]],"date-time":"2007-03-19T20:35:15Z","timestamp":1174336515000},"page":"292-300","source":"Crossref","is-referenced-by-count":14,"title":["C620R mutation of the murine <i>ret<\/i> proto\u2010oncogene: Loss of function effect in homozygotes and possible gain of function effect in heterozygotes"],"prefix":"10.1002","volume":"121","author":[{"given":"Luo","family":"Yin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldamaria","family":"Puliti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Bonora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Evangelisti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Conti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Min","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Jacques","family":"Medard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010France","family":"Lavou\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Forey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily 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