{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:20:10Z","timestamp":1790932810418,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,4,3]],"date-time":"2003-04-03T00:00:00Z","timestamp":1049328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis 2 (NF2) is a genetic disease that occurs in approximately 1 in 40,000 live births. Almost all affected individuals develop bilateral tumors of Schwann cells that surround the vestibular nerves; these tumors are known as vestibular schwannomas (VS). Evidence from molecular genetic studies suggests that at least two mutations are involved in formation of VS in patients with NF2. Several authors proposed probabilistic models for this process in other tumors, and showed that such models are consistent with incidence data. We evaluated two different probabilistic models for a \u201c2\u2010hit\u201d hypothesis for VS development in NF2 patients, and we present results from fitting these models to incidence data. Molecular evidence does not exclude the possibility that additional hits are necessary for the development of VS, and we also assessed a \u201c3\u2010hit\u201d model for tumor formation. The \u201c3\u2010hit\u201d model fits the data marginally better than one of the \u201c2\u2010hit\u201d models and much better than the other \u201c2\u2010hit\u201d model. Our findings suggest that more than two mutations may be necessary for VS development in NF2 patients. <jats:italic>Genet Epidemiol<\/jats:italic> 24:265\u2013272, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gepi.10238","type":"journal-article","created":{"date-parts":[[2003,4,7]],"date-time":"2003-04-07T15:03:08Z","timestamp":1049727788000},"page":"265-272","source":"Crossref","is-referenced-by-count":28,"title":["Exploring the \u201ctwo\u2010hit hypothesis\u201d in NF2: Tests of two\u2010hit and three\u2010hit models of vestibular schwannoma development"],"prefix":"10.1002","volume":"24","author":[{"given":"Ryan","family":"Woods","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Gareth R","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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