Intraneural and sclerosing perineuriomas display similar NF2 gene alterations as seen in meningioma, indicating a similar pathogenesis and molecular homology.
Mutations in the tumor suppressor gene coding for merlin cause Neurofibromatosis type 2 (NF2), all spontaneous schwannomas, and a majority of meningiomas.
Analogous to merlin, we show that DAL-1 loss is an early event in meningioma tumorigenesis, suggesting that these two protein 4.1 family members are critical growth regulators in the pathogenesis of meningiomas.
Mutations in the neurofibromatosis 2 (NF2) gene are the predominant cause in the development of sporadic schwannomas and are also involved in the pathogenesis of meningiomas and ependymomas.
We identified over 2000 proteins in comparative experiments between Merlin-deficient schwannoma and meningioma compared to human Schwann and meningeal cells respectively.
In addition, a strong overexpression of PrP<sup>C</sup> is observed in human Merlin-deficient mesothelioma cell line TRA and in human Merlin-deficient meningiomas.
Loss-of-function mutations or deletion of the NF2 gene, resulting in loss of the encoded Merlin protein, lead to Neurofibromatosis type 2 (NF2), but also cause the formation of sporadic meningiomas.
Our patient demonstrates the need for molecular testing for NF2 gene mutations even in isolated childhood meningiomas although they do not fulfill the clinical criteria of NF2.
Because group I p21-activated kinases (Paks) bind to and are inhibited by the NF2-encoded protein Merlin, we assessed the signaling and anti-tumor effects of three group-I specific Pak inhibitors - Frax597, 716 and 1036 - in NF2-/- meningiomas in vitro and in an orthotopic mouse model.
Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas, thus supporting the hypothesis that the NF2 gene is also important in meningioma pathogenesis.
These results provide strong evidence that the suppressor gene on chromosome 22, frequently inactivated in meningioma, is the NF2 gene, and suggest that another gene is involved in the development of 40% of meningiomas.
These data strongly support the notion that NF2 is the sole target of 22q LOH in meningiomas and that loss of merlin expression is always caused by genetic alteration of NF2, following the classic "two hit" theory.
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.
Alterations in the NF2 gene coding for merlin cause all tumours that occur in patients suffering from neurofibromatosis type 2, all spontaneous schwannomas and the majority of meningiomas.