Frequency and distribution of NF2 mutations in schwannomas

Genes Chromosomes Cancer. 1996 Sep;17(1):45-55. doi: 10.1002/(SICI)1098-2264(199609)17:1<45::AID-GCC7>3.0.CO;2-2.


Sporadic and inherited schwannomas were scanned for the nature, frequency, and distribution of mutations in the NF2 locus encoding the merlin tumor suppressor protein on 22q. Of 58 tumors, 47% displayed loss of heterozygosity for NF2, leaving a total of 89 NF2 alleles to be examined. Pathogenic alterations were identified in 62 of these alleles, including 36 frameshifts with premature termination, 14 nonsense mutations, and 12 changes presumed to affect splicing. Effects of ten of the latter were confirmed in the NF2 transcript and indicated that activation of cryptic splice sites in coding sequence is another frequent mechanism leading to truncation of merlin. The mutations were relatively evenly distributed across both the protein 4.1 superfamily (exons 1-9) and the alpha-helical (exons 10-15) domains of merlin, but they did not occur at all in exons 16 and 17, which encode the protein's alternative COOH-termini. The data support the "two-hit" tumor suppressor model for formation of schwannomas and indicate that loss of merlin function can be achieved by truncation at various locations in the protein. However, the absence of mutations in exons 16 and 17 suggests that an inactivating mutation affecting only one of the merlin's alternative termini may not be sufficient to eliminate tumor suppressor function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Chromosomes, Human, Pair 22*
  • Exons
  • Female
  • Genes, Neurofibromatosis 2 / genetics*
  • Genotype
  • Humans
  • Male
  • Membrane Proteins
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins
  • Neurilemmoma / genetics*
  • Neurofibromin 2
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA


  • Membrane Proteins
  • Neoplasm Proteins
  • Neurofibromin 2