title: The neurofibromatosis type 2 gene is inactivated in schwannomas.
abstract: Schwannomas are tumors arising from schwann cells surrounding peripheral nerves. Although most schwannomas are sporadic, they are seen in approximately 90% of individuals with neurofibromatosis type 2 (NF2), an autosomal dominantly inherited disease with an incidence of 1:40000 live births. The NF2 gene has recently been isolated on chromosome 22 and encodes a putative membrane organizing protein named schwannomin. It is believed to act as a tumor suppressor gene based on the high frequency of loss of heterozygosity (LOH) on this autosome in both sporadic and NF2 associated schwannomas and meningiomas and the identification of inactivating mutation in NF2 patients. In this study we examined 61 schwannomas including 48 sporadic schwannomas (46 of which are vestibular schwannomas) and 12 schwannomas obtained from NF2 patients, for mutations in 10 of the 16 coding exons of the NF2 gene. Twelve inactivating mutations were identified, 8 in sporadic tumours and 4 in tumors from people with NF2. These results support the hypothesis that loss of function of schwannomin is a frequent and fundamental event in the genesis of schwannomas.
authors.affiliation: Centre for Research in Neuroscience, McGill University, Montreal, Canada.
authors.forename: E C
authors.initials: EC
authors.lastname: Twist
authors.forename: M H
authors.initials: MH
authors.lastname: Ruttledge
authors.forename: M
authors.initials: M
authors.lastname: Rousseau
authors.forename: M
authors.initials: M
authors.lastname: Sanson
authors.forename: L
authors.initials: L
authors.lastname: Papi
authors.forename: P
authors.initials: P
authors.lastname: Merel
authors.forename: O
authors.initials: O
authors.lastname: Delattre
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D015994:Incidence; D008565:Membrane Proteins / Q000235:genetics*; D008577:Meningeal Neoplasms / Q000235:genetics; D008579:Meningioma / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009442:Neurilemmoma / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016518:Neurofibromatosis 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D025581:Neurofibromin 2; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D025581:Neurofibromin 2