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  • Title: Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin.
    Author: Robanus-Maandag E, Giovannini M, van der Valk M, Niwa-Kawakita M, Abramowski V, Antonescu C, Thomas G, Berns A.
    Journal: Oncogene; 2004 Aug 26; 23(39):6541-7. PubMed ID: 15221010.
    Abstract:
    Previously, we have mimicked human neurofibromatosis type 2 (NF2) in conditional Nf2 mutant (P0Cre;Nf2flox2/flox2) mice. Schwannomas, characteristic for NF2, were found at low frequency in older mice. Here, we report that these mice, upon additional hemizygosity for p53, rapidly develop multiple tumours showing features consistent with malignant peripheral nerve sheath tumours. Thus, p53 hemizygosity promotes tumorigenesis of mutant Nf2 peripheral nerve cells. In contrast, young P0Cre;Nf2flox2/+;p53+/- cis mice mainly succumb to Nf2/p53-related osteogenic tumours. Therefore, Cre-mediated early biallelic loss of Nf2 function in neural crest-derived cells hemizygous for p53 results in resistance to osteogenic tumours and increased susceptibility to peripheral nerve sheath tumours.
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