These results provide additional evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas and schwannomas.
Subjects who inherit a mutated allele of the NF2 gene inevitably develop schwannomas, affecting particularly the superior vestibular branch of the 8th cranial nerve, usually bilaterally.
Germ-line mutations in the neurofibromatosis 2 (NF2) gene cause a susceptibility to the development of schwannoma and meningioma, 2 mostly benign tumors of neural crest origin.
NF2 gene mutations have been identified in the majority of sporadic and NF2-associated schwannomas and NF2 gene mutations have been shown to result in merlin protein phosphorylation.
From 17 of 19 tumors (14 meningiomas and five schwannomas), 12 of which have previously been shown to harbor truncating NF2 mutations, wild-type NF2 protein was immunoprecipitated.
Two tumor types that have been linked to specific gene alterations are schwannomas, which have mutations in the neurofibromatosis (NF) type 2 (NF2) gene, and neurofibromas, which characteristically possess NF type 1 (NF1) gene mutations.
We have extended these studies by screening virtually all coding sequences of the SCH gene (95% coverage) and adjacent splice site sequences for the presence of mutations in 48 schwannomas.
Molecular genetic analysis by temperature gradient gel electrophoresis and microsatellite marker analysis demonstrated two distinct mutations of the NF2 gene (NF2) in two different schwannomas, with concomitant loss of heterozygosity in both tumours.
As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges.
By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients.
Loss of the NF2 protein product, Merlin, is universal in both sporadic and NF2-related schwannomas and the loss or mutation of the gene is the only established causative event underlying schwannoma formation.
The genetic alterations observed in the NF2 gene indicated that spinal schwannomas are associated with genetic alterations also found in other schwannomas and type 2 Neurofibromatosis, which reinforces the etiological role of this gene.
Mutational inactivation of the <i>NF2</i> gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear.
We conclude that the involvement of the NF2 gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two-hit process.
Merlin has multiple functions, including within the nucleus and at the cell membrane, and this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention.
We identified over 2000 proteins in comparative experiments between Merlin-deficient schwannoma and meningioma compared to human Schwann and meningeal cells respectively.
Deficiency of the tumor suppressor protein merlin leads to the development of benign tumors of the nervous system such as schwannomas, ependymomas and meningiomas.
We investigated the effect of curcumin (diferuloylmethane), a molecule with anti-inflammatory and antitumorigenic properties, on human schwannoma cell growth and the regulation of merlin by curcumin in both NF2 cells and neuroblastoma (non-NF2) cells.
Consistent with the observation that over-expression of merlin arrested cell growth at G1-phase, the current study indicates that merlin exerts its antiproliferative effect, at least in part, by maintaining p21 expression, and loss of p21 is a prominent feature of merlin deficient schwannomas.