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Exploring the “two‐hit hypothesis” in NF2: Tests of two‐hit and three‐hit models of vestibular schwannoma development
Author(s) -
Woods Ryan,
Friedman J. M.,
Evans D. Gareth R,
Baser Michael E.,
Joe Harry
Publication year - 2003
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.10238
Subject(s) - schwannoma , neurofibromatosis type 2 , vestibular system , neurofibromatosis , incidence (geometry) , probabilistic logic , vestibular schwannomas , medicine , genetic model , audiology , biology , computer science , pathology , genetics , artificial intelligence , gene , physics , optics
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 “2‐hit” 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 “3‐hit” model for tumor formation. The “3‐hit” model fits the data marginally better than one of the “2‐hit” models and much better than the other “2‐hit” model. Our findings suggest that more than two mutations may be necessary for VS development in NF2 patients. Genet Epidemiol 24:265–272, 2003. © 2003 Wiley‐Liss, Inc.