Familial meningioma: analysis of expression of neurofibromatosis 2 protein Merlin

Report of two cases

Marius Maxwell M.B.B.Chir, D.Phil.1, Sarah D. Shih D.D.S., D.M.Sc.1, Theofanis Galanopoulos B.S.1, E. Tessa Hedley-Whyte M.D.1, and G. Rees Cosgrove M.D., F.R.C.S.(C)1
View More View Less
  • 1 Neurosurgical Service and Department of Neuropathology, Massachusetts General Hospital, and Departments of Surgery and Pathology, Harvard Medical School, Boston, Massachusetts
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
USD  $45.00
USD  $515.00
USD  $612.00
Print or Print + Online Sign in

✓ Meningiomas are primarily benign brain tumors thought to arise through multistep tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The recently isolated neurofibromatosis 2 (NF2) tumor suppressor gene has been found to be mutated in a large proportion of meningiomas. Almost all cases of familial meningioma occur in association with NF2. Familial meningioma in isolation from NF2 (sporadic) is exceedingly rare, with only 14 reports since 1959. The authors report the existence of a family lacking any stigmata of NF2, in which two members had spinal meningiomas. Tumor specimens were subjected to immunocytochemical analysis for the NF2 protein product Merlin, which has been implicated in the tumorigenesis of meningioma. Merlin immunoreactivity was present in both tumor specimens, implying that the NF2 tumor suppressor gene was not deleted in these tumors. This supports the hypothesis that a second tumor suppressor gene locus, other than NF2, acts in the formation of familial sporadic meningioma. The results are discussed in the context of putative oncogenic mechanisms of familial meningiomas.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
USD  $515.00
USD  $612.00
  • 1.

    Antoniades HN, Galanopoulos T, Neville-Golden J, et al: Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry. Int J Cancer 50:215222, 1992 Antoniades HN, Galanopoulos T, Neville-Golden J, et al: Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry. Int J Cancer 50:215–222, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Arakawa H, Hayashi N, Nagase H, et al: Alternative splicing of the NF2 gene and its mutation analysis of breast and colorectal cancers. Hum Mol Genet 3:565568, 1994 Arakawa H, Hayashi N, Nagase H, et al: Alternative splicing of the NF2 gene and its mutation analysis of breast and colorectal cancers. Hum Mol Genet 3:565–568, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Bianchi AB, Hara T, Ramesh V, et al: Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet 6:185192, 1994 Bianchi AB, Hara T, Ramesh V, et al: Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet 6:185–192, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Bishop JM: Molecular themes in oncogenesis. Cell 64:235248, 1991 Bishop JM: Molecular themes in oncogenesis. Cell 64:235–248, 1991

  • 5.

    Bolger GB, Stamberg J, Kirsch IR, et al: Chromosome translocation t(14;22) and oncogene (c-sis) variant in a pedigree with familial meningioma. N Engl J Med 312:564567, 1985 Bolger GB, Stamberg J, Kirsch IR, et al: Chromosome translocation t(14;22) and oncogene (c-sis) variant in a pedigree with familial meningioma. N Engl J Med 312:564–567, 1985

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Carstens C, Messe E, Zang KD, et al: Human KRAS oncogene expression in meningioma. Cancer Lett 43:3741, 1988 Carstens C, Messe E, Zang KD, et al: Human KRAS oncogene expression in meningioma. Cancer Lett 43:37–41, 1988

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Dumanski JP, Rouleau GA, Nordenskjöld M, et al: Molecular genetic analysis of chromosome 22 in 81 cases of meningioma. Cancer Res 50:58635867, 1990 Dumanski JP, Rouleau GA, Nordenskjöld M, et al: Molecular genetic analysis of chromosome 22 in 81 cases of meningioma. Cancer Res 50:5863–5867, 1990

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61:759767, 1990 Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61:759–767, 1990

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Ferrante L, Mastronardi L, Acqui M, et al: Familial meningiomas. Report of two cases. J Neurosurg Sci 31:177182, 1987 Ferrante L, Mastronardi L, Acqui M, et al: Familial meningiomas. Report of two cases. J Neurosurg Sci 31:177–182, 1987

    • Search Google Scholar
    • Export Citation
  • 10.

    Gaist G, Piazza G: Meningiomas in two members of the same family (with no evidence of neurofibromatosis). J Neurosurg 16:110113, 1959 Gaist G, Piazza G: Meningiomas in two members of the same family (with no evidence of neurofibromatosis). J Neurosurg 16:110–113, 1959

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Grunert V, Horcajada J, Sunder-Plassmann M: Familiäres Auftreten intrakranieller Meningeome. Wien Med Wochenschr 120:807808, 1970 Grunert V, Horcajada J, Sunder-Plassmann M: Familiäres Auftreten intrakranieller Meningeome. Wien Med Wochenschr 120:807–808, 1970

    • Search Google Scholar
    • Export Citation
  • 12.

    Hauge M, Harvald B: Studies in the etiology of intracranial tumours. Acta Psychiatr Neurol Scand 35:163170, 1960 Hauge M, Harvald B: Studies in the etiology of intracranial tumours. Acta Psychiatr Neurol Scand 35:163–170, 1960

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Huynh DP, Pulst SM: Neurofibromatosis 2 antisense oligodeoxynucleotides induce reversible inhibition of schwannomin synthesis and cell adhesion in STS26T and T98G cells. Oncogene 13:7384, 1996 Huynh DP, Pulst SM: Neurofibromatosis 2 antisense oligodeoxynucleotides induce reversible inhibition of schwannomin synthesis and cell adhesion in STS26T and T98G cells. Oncogene 13:73–84, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    James CD, Carlbom E, Dumanski JP, et al: Clonal genomic alterations in glioma malignancy stages. Cancer Res 48:55465551, 1988 James CD, Carlbom E, Dumanski JP, et al: Clonal genomic alterations in glioma malignancy stages. Cancer Res 48:5546–5551, 1988

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Joseph JT, Lisle DK, Jacoby LB, et al: NF2 gene analysis distinguishes hemangiopericytoma from meningioma. Am J Pathol 147:14501455, 1995 Joseph JT, Lisle DK, Jacoby LB, et al: NF2 gene analysis distinguishes hemangiopericytoma from meningioma. Am J Pathol 147:1450–1455, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Joynt RJ, Perret GE: Familial meningiomas. J Neurol Neurosurg Psychiatry 28:163164, 1965 Joynt RJ, Perret GE: Familial meningiomas. J Neurol Neurosurg Psychiatry 28:163–164, 1965

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Joynt RJ, Perret GE: Meningiomas in a mother and daughter. Cases without evidence of neurofibromatosis. Neurology 11:164165, 1961 Joynt RJ, Perret GE: Meningiomas in a mother and daughter. Cases without evidence of neurofibromatosis. Neurology 11:164–165, 1961

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Larson JJ, Tew JM Jr, Simon M, et al: Evidence for clo-nal spread in the development of multiple meningiomas. J Neurosurg 83:705709, 1996 Larson JJ, Tew JM Jr, Simon M, et al: Evidence for clo-nal spread in the development of multiple meningiomas. J Neurosurg 83:705–709, 1996

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Lekanne Deprez RH, Riegman PHJ, Groen NA, et al: Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma. Oncogene 10:15211528, 1995 Lekanne Deprez RH, Riegman PHJ, Groen NA, et al: Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma. Oncogene 10:1521–1528, 1995

    • Search Google Scholar
    • Export Citation
  • 20.

    Lindblom A, Ruttledge M, Collins VP, et al: Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression. Int J Cancer 56:354357, 1994 Lindblom A, Ruttledge M, Collins VP, et al: Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression. Int J Cancer 56:354–357, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Luna EJ, Hitt AL: Cytoskeleton-plasma membrane interactions. Science 258:955964, 1992 Luna EJ, Hitt AL: Cytoskeleton-plasma membrane interactions. Science 258:955–964, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Lutchman M, Rouleau GA: The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells. Cancer Res 55:22702274, 1995 Lutchman M, Rouleau GA: The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells. Cancer Res 55:2270–2274, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Maxwell M, Galanopoulos T, Antoniades HN: Coexpression of EGFR and TGFα mRNA and protein occurs in primary meningiomas. Int J Oncol 9:917922, 1996 Maxwell M, Galanopoulos T, Antoniades HN: Coexpression of EGFR and TGFα mRNA and protein occurs in primary meningiomas. Int J Oncol 9:917–922, 1996

    • Search Google Scholar
    • Export Citation
  • 24.

    Maxwell M, Galanopoulos T, Antoniades HN: Expression of cyclin D1 proto-oncogene mRNA in primary meningiomas may contribute to tumorigenesis. Int J Oncol 9:12131217, 1996 Maxwell M, Galanopoulos T, Antoniades HN: Expression of cyclin D1 proto-oncogene mRNA in primary meningiomas may contribute to tumorigenesis. Int J Oncol 9:1213–1217, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Maxwell M, Galanopoulos T, Hedley-Whyte ET, et al: Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products. Int J Cancer 46:1621, 1990 Maxwell M, Galanopoulos T, Hedley-Whyte ET, et al: Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products. Int J Cancer 46:16–21, 1990

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Maxwell M, Galanopoulos T, Neville-Golden J, et al: Expression of androgen and progesterone receptors in primary human meningiomas. J Neurosurg 78:456462, 1993 Maxwell M, Galanopoulos T, Neville-Golden J, et al: Expression of androgen and progesterone receptors in primary human meningiomas. J Neurosurg 78:456–462, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Mehta D, Khatib R, Patel S, et al: Carcinoma of the breast and meningioma. Association and management. Cancer 51:19371940, 1983 Mehta D, Khatib R, Patel S, et al: Carcinoma of the breast and meningioma. Association and management. Cancer 51:1937–1940, 1983

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Memon MY: Multiple and familial meningiomas without evidence of neurofibromatosis. Neurosurgery 7:262264, 1980 Memon MY: Multiple and familial meningiomas without evidence of neurofibromatosis. Neurosurgery 7:262–264, 1980

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Mikkelsen T, Cairncross JG, Cavenee WK: Genetics of the malignant progression of astrocytoma. J Cell Biochem 46:38, 1991 Mikkelsen T, Cairncross JG, Cavenee WK: Genetics of the malignant progression of astrocytoma. J Cell Biochem 46:3–8, 1991

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Mirimanoff RO, Dosoretz DE, Linggood RM, et al: Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:1824, 1985 Mirimanoff RO, Dosoretz DE, Linggood RM, et al: Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:18–24, 1985

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Pulst SM, Rouleau GA, Marineau C, et al: Familial meningioma is not allelic to neurofibromatosis 2. Neurology 43:20962098, 1993 Pulst SM, Rouleau GA, Marineau C, et al: Familial meningioma is not allelic to neurofibromatosis 2. Neurology 43:2096–2098, 1993

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Rempel SA, Schwechheimer K, Davis RL, et al: Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression. Cancer Res 53:23862392, 1993 Rempel SA, Schwechheimer K, Davis RL, et al: Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression. Cancer Res 53:2386–2392, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Rouleau GA, Merel P, Lutchman M, et al: Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:515521, 1993 Rouleau GA, Merel P, Lutchman M, et al: Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:515–521, 1993

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Russell DS, Rubinstein LJ: Pathology of Tumours of the Nervous System, ed 5. Baltimore: Williams & Wilkins, 1989, pp 453532 Russell DS, Rubinstein LJ: Pathology of Tumours of the Nervous System, ed 5. Baltimore: Williams & Wilkins, 1989, pp 453–532

    • Search Google Scholar
    • Export Citation
  • 35.

    Ruttledge MH, Sarrazin J, Rangaratnam S, et al: Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet 6:180184, 1994 Ruttledge MH, Sarrazin J, Rangaratnam S, et al: Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet 6:180–184, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Sahar A: Familial occurrence of meningiomas. Case report. J Neurosurg 23:444445, 1965 Sahar A: Familial occurrence of meningiomas. Case report. J Neurosurg 23:444–445, 1965

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Sato N, Yonemura S, Obinata T, et al: Radixin, a barbed end-capping actin-modulating protein, is concentrated in the cleavage furrow during cytokinesis. J Cell Biol 113:321330, 1991 Sato N, Yonemura S, Obinata T, et al: Radixin, a barbed end-capping actin-modulating protein, is concentrated in the cleavage furrow during cytokinesis. J Cell Biol 113:321–330, 1991

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Sedzimir CB, Frazer AK, Roberts JR: Cranial and spinal meningiomas in a pair of identical twin boys. J Neurol Neursurg Psychiatry 36:368376, 1973 Sedzimir CB, Frazer AK, Roberts JR: Cranial and spinal meningiomas in a pair of identical twin boys. J Neurol Neursurg Psychiatry 36:368–376, 1973

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Seizinger BR, de la Monte S, Atkins L, et al: Molecular genetic approach to human meningioma: loss of genes on chromosome 22. Proc Natl Acad Sci USA 84:54195423, 1987 Seizinger BR, de la Monte S, Atkins L, et al: Molecular genetic approach to human meningioma: loss of genes on chromosome 22. Proc Natl Acad Sci USA 84:5419–5423, 1987

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Sieb JP, Pulst SM, Buch A: Familial CNS tumors. J Neurol 239:343344, 1992 Sieb JP, Pulst SM, Buch A: Familial CNS tumors. J Neurol 239:343–344, 1992

  • 41.

    Trofatter JA, MacCollin MM, Rutter JL, et al: A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:791800, 1993 Trofatter JA, MacCollin MM, Rutter JL, et al: A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:791–800, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Twist EC, Ruttledge MH, Rousseau M, et al: The neurofibromatosis type 2 gene is inactivated in schwannomas. Hum Mol Genet 3:147151, 1994 Twist EC, Ruttledge MH, Rousseau M, et al: The neurofibromatosis type 2 gene is inactivated in schwannomas. Hum Mol Genet 3:147–151, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Van Landegem W, Vakaet A, De Paepe A, et al: Familial meningioma. Case report with cytogenetic study. Clin Neurol Neurosurg 90:6163, 1988 Van Landegem W, Vakaet A, De Paepe A, et al: Familial meningioma. Case report with cytogenetic study. Clin Neurol Neurosurg 90:61–63, 1988

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Wang JL, Nistér M, Hermansson M, et al: Expression of PDGF ß-receptors in human meningioma cells. Int J Cancer 46:772778, 1990 Wang JL, Nistér M, Hermansson M, et al: Expression of PDGF ß-receptors in human meningioma cells. Int J Cancer 46:772–778, 1990

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45.

    Wang JL, Zhang ZJ, Hartman M, et al: Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples. Int J Cancer 64:223228, 1995 Wang JL, Zhang ZJ, Hartman M, et al: Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples. Int J Cancer 64:223–228, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Wellenreuther R, Kraus JA, Lenartz D, et al: Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma. Am J Pathol 146:827832, 1995 Wellenreuther R, Kraus JA, Lenartz D, et al: Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma. Am J Pathol 146:827–832, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Wieczorek V, Tinschert K, Behrendt W, et al: Familiäres Auftreten von multiplen, vorwiegend spinalen Meningiomen. Nervenarzt 63:244246, 1992 Wieczorek V, Tinschert K, Behrendt W, et al: Familiäres Auftreten von multiplen, vorwiegend spinalen Meningiomen. Nervenarzt 63:244–246, 1992

    • Search Google Scholar
    • Export Citation
  • 48.

    Zhao JF, Sharma S: Expression of the ROS1 oncogene for tyrosine receptor kinase in adult human meningiomas. Cancer Genet Cytogenet 83:148154, 1995 Zhao JF, Sharma S: Expression of the ROS1 oncogene for tyrosine receptor kinase in adult human meningiomas. Cancer Genet Cytogenet 83:148–154, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Zulch KJ: Histological Typing of Tumors of the Central Nervous System. International Histological Classification of Tumors. Geneva: World Health Organization, 1979 Zulch KJ: Histological Typing of Tumors of the Central Nervous System. International Histological Classification of Tumors. Geneva: World Health Organization, 1979

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 512 105 24
Full Text Views 177 2 0
PDF Downloads 105 4 0
EPUB Downloads 0 0 0