The neurofibromatosis 2 (NF2) tumor suppressor gene product, merlin (schwannomin) forms an intramolecular association that is required for negative growth regulation in vitro and in vivo.
However, contrary to activation of mTORC1, the attenuated mTORC2 signaling profiles exhibited by normal arachnoid and Schwann cells in response to acute merlin loss were not consistently reflected in NF2-deficient meningiomas and schwannomas, suggesting additional genetic events may have been acquired in tumors after initial merlin loss.
Our findings in primary schwannoma cells from NF2 patients strongly support the hypothesis of merlin acting as a tumour suppressor and may help in understanding development of human schwannomas in NF2.
The specific association of eye abnormalities and NF2 might be caused by a genetic change on chromosome 22 that affects both the NF2 gene and a physically linked crystallin gene.
Finally, depletion of DCAF1 inhibits the hyperproliferation of Schwannoma cells from NF2 patients and suppresses the oncogenic potential of Merlin-deficient tumor cell lines.
Because Merlin, the affected tumour suppressor gene in NF2, is also known to be involved in stabilizing membrane-cytoskeletal complexes, as well as in cell proliferation, and apoptosis, we looked for potentially common mechanisms of action in the agents' effects on NF1 and NF2.
Further, we performed fluorescence in situ hybridization analysis with a genomic BAC clone harboring the NF2 gene and found that the 5 tumors with loss detected by CGH as well as three cases without such a detectable loss by CGH, or a total, 8/17 (47%), showed loss of the NF2 locus.
Blood samples from 125 unrelated families with classical type 2 neurofibromatosis (NF2) with bilateral vestibular schwannomas have been analysed for mutations in the NF2 gene.
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.
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.
Some of these tumors show an altered neurofibromatosis type 2 (NF2) gene; in others, NF2 appears to be unaffected, indicating the involvement of another tumor suppressor gene.
Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors.