NEUROFIBROMATOSIS TYPE-2 - A NEW MECHANISM OF TUMOR SUPPRESSION

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes primarily to CNS tumors such as schwannomas (vestibular an d spinal), meningiomas, ependymomas and juvenile posterior lenticular opacities. Allelic losses on chromosome 22q first suggested the existe nce of a tumor suppressor on this autosome in accordance with Knudson' s 'two hit' model, The gene was identified by positional cloning and f ound to encode a novel protein schwannomin (also known as merlin), wit h high sequence similarity to the band 4.1 family of proteins,This sim ilarity suggested a new mechanism of tumor suppression since it was th e first time a structural protein had been associated with a human tum or, Mutation analysis confirmed that inactivation of the NF2 gene occu rred in NF2 tumors and a majority of sporadic schwannomas and meningio mas, Expression and functional studies have provided additional inform ation on the possible involvement of this novel tumor suppressor in ce ll differentiation, embryogenesis and growth suppression.