Intraneural and sclerosing perineuriomas display similar NF2 gene alterations as seen in meningioma, indicating a similar pathogenesis and molecular homology.
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.
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.
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.
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.
Defects caused by mutations of the NF2 gene give rise to NF2 disease, which is generally characterized by the formation of bilateral vestibular schwannomas and, to a lesser extent, meningiomas and ependymomas.
Fluorescence in situ hybridization for chromosome 22 confirmed high allele loss involving the neurofibromin 2 gene locus, a finding typical in meningiomas.
These results provide evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas as well as indicating a different tumorigenesis of these meningioma variants.
The best defined of these syndromes is neurofibromatosis type 2, which is caused by a mutation in the NF2 gene and has a meningioma incidence of approximately 50%.
These results provide additional evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas and schwannomas.
Meningiomas are common primary brain tumours frequently presenting with deleted and/or mutated NF2 gene located on 22q.1p has been reported as the second most commonly deleted chromosomal region in these neoplasms.
Our findings confirm that the NF2 gene plays a role in the tumorigenesis of pediatric meningiomas and that chromogenic in situ hybridization is an efficient, economic, and reliable method for routinely assessing NF2 gene deletion in formalin-fixed, paraffin-embedded tissues.
We analysed 23 sporadic schwannomas for mutations in the NF2 gene and for the allelic status at 1p, 14q and 22q, as alterations of these genomic regions appear to be related to tumour progression in meningiomas, another NF2-associated neoplasm.
All VS and many meningiomas result from loss of the neurofibromatosis type 2 (NF2) gene product merlin, with ensuing PAK hyperactivation and increased cell proliferation/survival.