Skip to main content
NCBI home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;16(1):15–19. doi: 10.1111/j.1750-3639.2006.tb00557.x

NF2 Mutations in Secretory and Other Rare Variants of Meningiomas

Christian Hartmann 1,✉, Jennifer Sieberns 1, Claire Gehlhaar 1, Matthias Simon 2, Werner Paulus 3, Andreas von Deimling 1
PMCID: PMC8095906  PMID: 16612978

Abstract

The Who classification defines different histological variants of meningiomas. Mutations of the tumor suppressor gene NF2 on 22q have been described in 30% to 60 % of sporadic meningiomas. however, the vast majority of the meningiomas that have been subject to NF2 analysis belong to the most frequent variants like transitional, fibroblastic and meningothelial meningiomas. Within these subtypes, transitional and fibroblastic meningiomas harbor significantly more NF2 mutations than meningothelial meningiomas, indicating molecular subsets of these tumors. to determine whether rare meningioma variants carry NF2 mutations we analyzed 80 tumors. NF2 mutations were detected in 5(36%) of 14psammomatous, 1 (11%) of 9 angiomatous, 2 (22%) of 9 clear cell, 1 (33%) of 3 chordoid and 1 (100%) of 1 papillary meningioma. In the single papillary meningioma, 2 different NF2 mutations were observed. no NF2 mutations were found in 33 secretory, 7 microcystic, 2 lymphoplasmacyte‐rich, one rhabdoid and one metaplastic meningioma. In the control group of 25 fibroblastic meningiomas, 11 cases were identified to carry an NF2 mutation. These results support the concept of different molecular subgroups of meningiomas which overlap with histological variants.

References

  • 1. Bagnall KM, Higgins SJ, Sanders EJ (1988) The contribution made by a single somite to the vertebral column: experimental evidence in support of resegmentation using the chick‐quail chimaera model. Development 103:69–85. [DOI] [PubMed] [Google Scholar]
  • 2. Catala M (1998) Embryonic and fetal development of structures associated with the cerebro‐spinal fluid in man and other species. Part I: The ventricular system, meninges and choroid plexuses. Arch Anat Cytol Pathol 46:153–169. [PubMed] [Google Scholar]
  • 3. Couly GF, Coltey PM, Le Douarin, NM (1992) The developmental fate of the cephalic mesoderm in quail‐chick chimeras. Development 114:1–15. [DOI] [PubMed] [Google Scholar]
  • 4. De Vitis LR, Tedde A, Vitelli F, Ammannati F, Mennonna P, Bigozzi U, Montali E, Papi L (1996) Screening for mutations in the neurofibromatosis type 2 (NF2) gene in sporadic meningiomas. Hum Genet 97:632–637. [DOI] [PubMed] [Google Scholar]
  • 5. Evans JJ, Jeun SS, Lee JH, Harwalkar JA, Shoshan Y, Cowell JK, Golubic M (2001) Molecular alterations in the neurofibromatosis type 2 gene and its protein rarely occurring in meningothelial meningiomas. J Neurosurg 94:111–117. [DOI] [PubMed] [Google Scholar]
  • 6. Gallagher PG (2004) Hereditary elliptocytosis: spectrin and protein 4.1R. Semin Hematol 41:142–164. [DOI] [PubMed] [Google Scholar]
  • 7. Halata Z, Grim M, Christ B (1990) Origin of spinal cord meninges, sheaths of peripheral nerves, and cutaneous receptors including Merkel cells. An experimental and ultrastructural study with avian chimeras. Anat Embryol (Berl) 182:529–537. [DOI] [PubMed] [Google Scholar]
  • 8. Harada T, Irving RM, Xuereb JH, Barton DE, Hardy DG, Moffat DA, Maher ER (1996) Molecular genetic investigation of the neurofibromatosis type 2 tumor suppressor gene in sporadic meningioma. J Neurosurg 84:847–851. [DOI] [PubMed] [Google Scholar]
  • 9. Johnston MC (1966) A radioautographic study of the migration and fate of cranial neural crest cells in the chick embryo. Anat Rec 156:143–155. [DOI] [PubMed] [Google Scholar]
  • 10. Kleihues P, Cavenee WK (2000) Pathology and genetics of tumours of the nervous system. IARC Press: Lyon . [Google Scholar]
  • 11. Kros J, de Greve K, van Tilborg A, Hop W, Pieterman H, Avezaat C, Lekanne, Dit . Deprez, R , Zwarthoff E (2001) NF2 status of meningiomas is associated with tumour localization and histology. J Pathol 194:367–372. [DOI] [PubMed] [Google Scholar]
  • 12. Lamszus K (2004) Meningioma pathology, genetics, and biology. J Neuropathol Exp Neurol 63:275–286. [DOI] [PubMed] [Google Scholar]
  • 13. Lee JH, Sundaram V, Stein DJ, Kinney SE, Stacey DW, Golubic M (1997) Reduced expression of schwannomin/merlin in human sporadic meningiomas. Neurosurgery 40:578–587. [DOI] [PubMed] [Google Scholar]
  • 14. Lekanne Deprez, RH , Bianchi AB, Groen NA, Seizinger BR, Hagemeijer A, van Drunen E, Boots‐ma D, Koper JW, Avezaat CJ, Kley N, et al (1994) Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas. Am J Hum Genet 54:1022–1029. [PMC free article] [PubMed] [Google Scholar]
  • 15. Louis DN, Ramesh V, Gusella JF (1995) Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors. Brain Pathol 5:163–172. [DOI] [PubMed] [Google Scholar]
  • 16. Merel P, Hoang‐Xuan K, Sanson M, Bijlsma E, Rouleau G, Laurent‐Puig P, Pulst S, Baser M, Lenoir G, Sterkers, JM (1995) Screening for germ‐line mutations in the NF2 gene. Genes Chromosomes Cancer 12:117–127. [DOI] [PubMed] [Google Scholar]
  • 17. Merel P, Hoang‐Xuan K, Sanson M, Moreau‐Aubry A, Bijlsma EK, Lazaro C, Moisan JP, Resche F, Nishisho I, Estivill X, et al (1995) Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas. Genes Chromosomes Cancer 13:211–216. [DOI] [PubMed] [Google Scholar]
  • 18. Papi L, De Vitis LR, Vitelli F, Ammannati F, Mennonna P, Montali E, Bigozzi U (1995) Somatic mutations in the neurofibromatosis type 2 gene in sporadic meningiomas. Hum Genet 95:347–351. [DOI] [PubMed] [Google Scholar]
  • 19. Perry A, Gutmann DH, Reifenberger G (2004) Molecular pathogenesis of meningiomas. J Neurooncol 70:183–202. [DOI] [PubMed] [Google Scholar]
  • 20. Probst‐Cousin S, Villagran‐Lillo R, Lahl R, Bergmann M, Schmid KW, Gullotta F (1997) Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases. Cancer 79:2003–2015. [DOI] [PubMed] [Google Scholar]
  • 21. Ruttledge MH, Sarrazin J, Rangaratnam S, Phelan CM, Twist E, Merel P, Delattre O, Thomas G, Nordenskjold M, Collins, VP (1994) Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet 6:180–184. [DOI] [PubMed] [Google Scholar]
  • 22. Ruttledge MH, Xie YG, Han FY, Peyrard M, Collins VP, Nordenskjold M, Dumanski JP (1994) Deletions on chromosome 22 in sporadic meningioma. Genes Chromosomes Cancer 10:122–130. [DOI] [PubMed] [Google Scholar]
  • 23. Ueki K, Wen‐Bin C, Narita Y, Asai A, Kirino T (1999) Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningiomas. Cancer Res 59:5995–5998. [PubMed] [Google Scholar]
  • 24. Wellenreuther R, Kraus JA, Lenartz D, Menon AG, Schramm J, Louis DN, Ramesh V, Gusella JF, Wiestler OD, von Deimling, A (1995) Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma. Am J Pathol 146:827–832. [PMC free article] [PubMed] [Google Scholar]
  • 25. Wellenreuther R, Waha A, Vogel Y, Lenartz D, Schramm J, Wiestler OD, von Deimling, A (1997) Quantitative analysis of neurofibromatosis type 2 gene transcripts in meningiomas supports the concept of distinct molecular variants. Lab Invest 77:601–606. [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES