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. 2005 Jan;42(1):45–48. doi: 10.1136/jmg.2004.023705

Multiple meningiomas: differential involvement of the NF2 gene in children and adults

D Evans 1, C Watson 1, A King 1, A Wallace 1, M Baser 1
PMCID: PMC1735900  PMID: 15635074

Abstract

Objective: To screen for NF2 mutations in people with meningiomas.

Methods: Lymphocyte or tumour DNA was analysed from 46 individuals from 36 families who presented with a meningioma at age ⩽15 years without vestibular schwannoma (VS), or who had multiple meningiomas in adulthood before the diagnosis of VS.

Results: Eight of 13 people with meningioma and other features of neurofibromatosis 2 (NF2) had an identified constitutional NF2 mutation in blood DNA, but none of the other subjects had identified constitutional NF2 mutations.

Conclusions: Constitutional NF2 mutations are the most likely cause of meningioma in children and in people with a meningioma plus other non-VS features of NF2. Mosaic NF2 may be the cause of about 8% of multiple meningiomas in sporadic adult cases, but there are other causes in the majority of other such patients and in multiple meningioma in families.

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Selected References

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  1. Antinheimo J., Sankila R., Carpén O., Pukkala E., Sainio M., Jäskeläinen J. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology. 2000 Jan 11;54(1):71–76. doi: 10.1212/wnl.54.1.71. [DOI] [PubMed] [Google Scholar]
  2. Bondy M., Ligon B. L. Epidemiology and etiology of intracranial meningiomas: a review. J Neurooncol. 1996 Sep;29(3):197–205. doi: 10.1007/BF00165649. [DOI] [PubMed] [Google Scholar]
  3. Evans D. G., Birch J. M., Ramsden R. T. Paediatric presentation of type 2 neurofibromatosis. Arch Dis Child. 1999 Dec;81(6):496–499. doi: 10.1136/adc.81.6.496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Evans D. G., Huson S. M., Donnai D., Neary W., Blair V., Newton V., Harris R. A clinical study of type 2 neurofibromatosis. Q J Med. 1992 Aug;84(304):603–618. [PubMed] [Google Scholar]
  5. Evans D. G., Huson S. M., Donnai D., Neary W., Blair V., Teare D., Newton V., Strachan T., Ramsden R., Harris R. A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet. 1992 Dec;29(12):841–846. doi: 10.1136/jmg.29.12.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans D. G., Wallace A. J., Wu C. L., Trueman L., Ramsden R. T., Strachan T. Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis. Am J Hum Genet. 1998 Sep;63(3):727–736. doi: 10.1086/512074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans J. J., Jeun S. S., Lee J. H., Harwalkar J. A., Shoshan Y., Cowell J. K., Golubic M. Molecular alterations in the neurofibromatosis type 2 gene and its protein rarely occurring in meningothelial meningiomas. J Neurosurg. 2001 Jan;94(1):111–117. doi: 10.3171/jns.2001.94.1.0111. [DOI] [PubMed] [Google Scholar]
  8. Gutmann D. H., Donahoe J., Perry A., Lemke N., Gorse K., Kittiniyom K., Rempel S. A., Gutierrez J. A., Newsham I. F. Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas. Hum Mol Genet. 2000 Jun 12;9(10):1495–1500. doi: 10.1093/hmg/9.10.1495. [DOI] [PubMed] [Google Scholar]
  9. Harada T., Irving R. M., Xuereb J. H., Barton D. E., Hardy D. G., Moffat D. A., Maher E. R. Molecular genetic investigation of the neurofibromatosis type 2 tumor suppressor gene in sporadic meningioma. J Neurosurg. 1996 May;84(5):847–851. doi: 10.3171/jns.1996.84.5.0847. [DOI] [PubMed] [Google Scholar]
  10. Heinrich Bianca, Hartmann Christian, Stemmer-Rachamimov Anat O., Louis David N., MacCollin Mia. Multiple meningiomas: Investigating the molecular basis of sporadic and familial forms. Int J Cancer. 2003 Feb 10;103(4):483–488. doi: 10.1002/ijc.10840. [DOI] [PubMed] [Google Scholar]
  11. Kros J., de Greve K., van Tilborg A., Hop W., Pieterman H., Avezaat C., Lekanne Dit Deprez R., Zwarthoff E. NF2 status of meningiomas is associated with tumour localization and histology. J Pathol. 2001 Jul;194(3):367–372. doi: 10.1002/path.909. [DOI] [PubMed] [Google Scholar]
  12. Kuratsu J., Kochi M., Ushio Y. Incidence and clinical features of asymptomatic meningiomas. J Neurosurg. 2000 May;92(5):766–770. doi: 10.3171/jns.2000.92.5.0766. [DOI] [PubMed] [Google Scholar]
  13. Lamszus K., Vahldiek F., Mautner V. F., Schichor C., Tonn J., Stavrou D., Fillbrandt R., Westphal M., Kluwe L. Allelic losses in neurofibromatosis 2-associated meningiomas. J Neuropathol Exp Neurol. 2000 Jun;59(6):504–512. doi: 10.1093/jnen/59.6.504. [DOI] [PubMed] [Google Scholar]
  14. Leone P. E., Bello M. J., de Campos J. M., Vaquero J., Sarasa J. L., Pestaña A., Rey J. A. NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas. Oncogene. 1999 Apr 1;18(13):2231–2239. doi: 10.1038/sj.onc.1202531. [DOI] [PubMed] [Google Scholar]
  15. Lomas Jesus, Bello M. Josefa, Alonso M. Eva, Gonzalez-Gomez Pilar, Arjona Dolores, Kusak M. Elena, de Campos Jose M., Sarasa Jose L., Rey Juan A. Loss of chromosome 22 and absence of NF2 gene mutation in a case of multiple meningiomas. Hum Pathol. 2002 Mar;33(3):375–378. doi: 10.1053/hupa.2002.32229. [DOI] [PubMed] [Google Scholar]
  16. Maxwell M., Shih S. D., Galanopoulos T., Hedley-Whyte E. T., Cosgrove G. R. Familial meningioma: analysis of expression of neurofibromatosis 2 protein Merlin. Report of two cases. J Neurosurg. 1998 Mar;88(3):562–569. doi: 10.3171/jns.1998.88.3.0562. [DOI] [PubMed] [Google Scholar]
  17. Moyhuddin A., Baser M. E., Watson C., Purcell S., Ramsden R. T., Heiberg A., Wallace A. J., Evans D. G. R. Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet. 2003 Jun;40(6):459–463. doi: 10.1136/jmg.40.6.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Perry A., Cai D. X., Scheithauer B. W., Swanson P. E., Lohse C. M., Newsham I. F., Weaver A., Gutmann D. H. Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. J Neuropathol Exp Neurol. 2000 Oct;59(10):872–879. doi: 10.1093/jnen/59.10.872. [DOI] [PubMed] [Google Scholar]
  19. Perry A., Giannini C., Raghavan R., Scheithauer B. W., Banerjee R., Margraf L., Bowers D. C., Lytle R. A., Newsham I. F., Gutmann D. H. Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: a clinicopathologic study of 53 cases. J Neuropathol Exp Neurol. 2001 Oct;60(10):994–1003. doi: 10.1093/jnen/60.10.994. [DOI] [PubMed] [Google Scholar]
  20. Pulst S. M., Rouleau G. A., Marineau C., Fain P., Sieb J. P. Familial meningioma is not allelic to neurofibromatosis 2. Neurology. 1993 Oct;43(10):2096–2098. doi: 10.1212/wnl.43.10.2096. [DOI] [PubMed] [Google Scholar]
  21. Sadetzki Siegal, Flint-Richter Pazit, Ben-Tal Tehila, Nass Dvora. Radiation-induced meningioma: a descriptive study of 253 cases. J Neurosurg. 2002 Nov;97(5):1078–1082. doi: 10.3171/jns.2002.97.5.1078. [DOI] [PubMed] [Google Scholar]
  22. Sulman E. P., Dumanski J. P., White P. S., Zhao H., Maris J. M., Mathiesen T., Bruder C., Cnaan A., Brodeur G. M. Identification of a consistent region of allelic loss on 1p32 in meningiomas: correlation with increased morbidity. Cancer Res. 1998 Aug 1;58(15):3226–3230. [PubMed] [Google Scholar]
  23. Wallace A. J., Wu C. L., Elles R. G. Meta-PCR: a novel method for creating chimeric DNA molecules and increasing the productivity of mutation scanning techniques. Genet Test. 1999;3(2):173–183. doi: 10.1089/gte.1999.3.173. [DOI] [PubMed] [Google Scholar]
  24. Zhu J. J., Maruyama T., Jacoby L. B., Herman J. G., Gusella J. F., Black P. M., Wu J. K. Clonal analysis of a case of multiple meningiomas using multiple molecular genetic approaches: pathology case report. Neurosurgery. 1999 Aug;45(2):409–416. doi: 10.1097/00006123-199908000-00049. [DOI] [PubMed] [Google Scholar]

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