Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin.
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.
Robanus-Maandag
Els
E
Division of Molecular Genetics, Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Giovannini
Marco
M
van der Valk
Martin
M
Niwa-Kawakita
Michiko
M
Abramowski
Vincent
V
Antonescu
Cristina
C
Thomas
Gilles
G
Berns
Anton
A
D000818:Animals; D016515:Genes, Neurofibromatosis 2; D016158:Genes, p53; D005838:Genotype; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D009442:Neurilemmoma / Q000235:genetics*