Somatic mutations in the neurofibromatosis type 2 gene in sporadic meningiomas

Hum Genet. 1995 Mar;95(3):347-51. doi: 10.1007/BF00225206.


Meningiomas are benign tumors of the central nervous system. Although usually sporadic, they can occur in patients affected by the autosomal dominant syndrome, neurofibromatosis type 2 (NF2). The NF2 gene has recently been isolated from chromosome 22. The presence of germline mutations in NF2 patients and the loss of heterozygosity (LOH) on 22q in NF2 tumors support the hypothesis that the NF2 gene acts as a tumor suppressor. Cytogenetic and LOH studies have suggested that the gene responsible for the development of meningiomas is located in the region of 22q in which the NF2 gene maps. The meningiomas gene could therefore be the NF2 gene itself. Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas, thus supporting the hypothesis that the NF2 gene is also important in meningioma pathogenesis. In this study, we analyzed sixty-one sporadic meningiomas for LOH of 22q and for mutations in the NF2 gene. LOH was detected in 36 of the 60 informative tumors. Single-strand conformational polymorphism analysis was used to identify nine mutations in five of the eight exons of the NF2 gene studied. The nine tumors with an altered NF2 gene also showed LOH for 22q markers. These results further support the hypothesis that mutations in the NF2 gene are a critical pathogenetic event in at least some meningiomas.

MeSH terms

  • Aged
  • Chromosome Deletion
  • Chromosomes, Human, Pair 22*
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Genes, Neurofibromatosis 2 / genetics*
  • Heterozygote
  • Humans
  • Male
  • Meningeal Neoplasms / genetics*
  • Meningioma / genetics*
  • Middle Aged
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational