Mutation Analysis in the NF2 Gene

摘要

To facilitate the search for mutations in neurofibromatosis 2 (NF2), we havedefined the exon-intron boundaries for the NF2 gene. PCR amplification of each exon in the NF2 gene combined with single strand conformation polymorphism (SSCP) analysis has identified a number of germline mutations in NF2-families and somatic alterations in sporadic vestibular schwannomas and meningiomas. Thus inactivation of the NF2 gene product merlin is a common feature underlying both inherited and sporadic forms of the NF2 related tumors. In order to understand the normal function of the NF2 protein merlin, we have generated a panel of monoclonal antibodies specific for merlin. Using indirect immunofluorescence and one of the monoclonal antibodies, we have for the first time visualized endogenous merlin and localized it to the motile regions, such as leading or ruffling edged, in human cells. Membrane ruffles are particularly seen at the leading edges of motile cells where they are believed to be required for directed cell migration. It is likely that merlin is important for cell movement, shape or communication. Investigation of these processes in Schwann cells and meningeal cells that are the targets of NF2 mutations may represent a fruitful avenue to elucidate the mechanism underlying the tumor suppressor function of merlin.