Skip to main content
SpringerLink
Log in

Biology and Genetics of Vestibular Schwannomas in Tumors of the Cerebellopontine Angle

  • Chapter
  • First Online:
Surgery of the Cerebellopontine Angle

  • 530 Accesses

Abstract

Advances in molecular biology have improved our understanding of the origin of vestibular schwannomas. The identification of mutations in the neurofibromatosis type 2 gene (NF2) as the underlying genetic cause of vestibular schwannomas has driven research into the molecular events leading to tumor formation. (Note: The italicized “NF2” represents the human neurofibromatosis type 2 gene specifically, while “NF2” is used to indicate the human disease of neurofibromatosis type 2, and “Nf2” indicates the homolog expressed in rodents). The clinical characteristics of both vestibular schwannomas and neurofibromatosis type 2 syndromes have been related to alterations in NF2. This gene encodes the protein “merlin,” a tumor suppressor that has been implicated in cell signaling pathways regulating growth and proliferation. These molecular studies have identified potential therapeutic targets, and here we review these recent advances in the context of vestibular schwannoma biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. National Institutes of Health. Acoustic neuroma. NIH Consens Statement. 1991;9:1–24.

    Google Scholar 

  2. Evans DGR. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis. 2009;4:16.

    Article  Google Scholar 

  3. Petrilli AM, Fernández-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2015;35:537–48.

    Article  Google Scholar 

  4. Howitz MF, Johansen TCM, Charabi S, Olsen JH. Incidence of vestibular schwannoma in Denmark, 1977-1995. Am J Otol. 2000;21:690–4.

    CAS  Google Scholar 

  5. Stangerup SE, Tos M, Thomsen J, Cayé-Thomasen P. True incidence of vestibular schwannoma? Neurosurgery. 2010;67:1335–40.

    Article  Google Scholar 

  6. Evans DG, Huson SM, 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;29:841–6.

    Article  CAS  Google Scholar 

  7. Schroeder RD, Angelo LS, Kurzrock R. NF2/merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations. Oncotarget. 2014;5:67–77.

    Article  Google Scholar 

  8. Berger AH, Knudson AG, Pandolfi PP. A continuum model for tumour suppression. Nature. 2011;476:163–9.

    Article  CAS  Google Scholar 

  9. Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68:820–3.

    Article  Google Scholar 

  10. Fontaine B, Rouleau GA, Seizinger BR, et al. Molecular genetics of neurofibromatosis 2 and related tumors (acoustic neuroma and meningioma). Ann NY Acad Sci. 1991;615:338–43.

    Google Scholar 

  11. Kaiser-Kupfer MI, Freidlin V, Datiles MB, et al. The association of posterior capsular lens opacities with bilateral acoustic neuromas in patients with neurofibromatosis type 2. Arch Ophthalmol. 1989;107:541–4.

    Google Scholar 

  12. Martuza RL, Eldridge R. Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Engl J Med. 1988;318:684–8.

    Google Scholar 

  13. Evans DG, Wallace AJ, Wu CL, et al. Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis. Am J Hum Genet. 1998;63:727–36.

    Google Scholar 

  14. Kluwe L, Mautner V, Heinrich B, et al. Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet. 2003;40:109–14.

    Google Scholar 

  15. Ruggieri M, Praticò AD, Serra A, et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital. 2016;36:345–67.

    Google Scholar 

  16. Moyhuddin A, Baser ME, Watson C, et al. Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet. 2003;40:459–63.

    Google Scholar 

  17. Evans DG, Bowers NL, Tobi S, et al. Schwannomatosis: a genetic and epidemiological study. J Neurol Neurosurg Psychiatry. 2018;89:1215–9.

    Google Scholar 

  18. MacCollin M, Willett C, Heinrich B, et al. Familial schwannomatosis: exclusion of the NF2 locus as the germline event. Neurology. 2003;60:1968–74.

    Google Scholar 

  19. Lee JD, Kwon TJ, Kim UK, Lee WS. Genetic and epigenetic alterations of the NF2 gene in sporadic vestibular schwannomas. PLoS One. 2012;7:e30418.

    Article  CAS  Google Scholar 

  20. Håvik HL, Bruland O, Myrseth E, et al. Genetic landscape of sporadic vestibular schwannoma. J Neurosurg. 2018;128:911–22.

    Article  Google Scholar 

  21. 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. 1993;363:515–21.

    Google Scholar 

  22. 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. 1993;72:791–800.

    Google Scholar 

  23. Welling DB, Guida M, Goll F, et al. Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and familial schwannomas. Hum Genet. 1996;98:189–93.

    Google Scholar 

  24. Welling DB. Clinical manifestations of mutations in the neurofibromatosis type 2 gene in vestibular schwannomas (acoustic neuromas). Laryngoscope. 1998;108:178–89.

    Article  CAS  Google Scholar 

  25. Irving RM, Harada T, Moffat DA, et al. Somatic neurofibromatosis type 2 gene mutations and growth characteristics in vestibular schwannoma. Am J Otol. 1997;18:754–60.

    Google Scholar 

  26. Jacoby LB, MacCollin M, Barone R, Ramesh V, Gusella JF. Frequency and distribution of NF2 mutations in schwannomas. Genes Chromosomes Cancer. 1996;17:45–55.

    Article  CAS  Google Scholar 

  27. Lasota J, Fetsch JF, Wozniak A, et al. The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases. Am J Pathol. 2001;158:1223–9.

    Google Scholar 

  28. Bianchi AB, Hara T, Ramesh V, et al. Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet. 1994;6:185–92.

    Google Scholar 

  29. 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. 1994;6:180–4.

    Google Scholar 

  30. Sekido Y, Pass HI, Bader S, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55:1227–31.

    Google Scholar 

  31. Sanson M, Marineau C, Desmaze C, et al. Germline deletion in a neurofibromatosis type 2 kindred inactivates the NF2 gene and a candidate meningioma locus. Hum Mol Genet. 1993;2:1215–20.

    Google Scholar 

  32. Hara T, Bianchi AB, Seizinger BR, Kley N. Molecular cloning and characterization of alternatively spliced transcripts of the mouse neurofibromatosis 2 gene. Cancer Res. 1994;54:330–5.

    CAS  Google Scholar 

  33. Jacoby LB, MacCollin M, Louis DN, et al. Exon scanning for mutation of the NF2 gene in schwannomas. Hum Mol Genet. 1994;3:413–9.

    Google Scholar 

  34. Pykett MJ, Murphy M, Harnish PR, George DL. The neurofibromatosis 2 (NF2) tumor suppressor gene encodes multiple alternatively spliced transcripts. Hum Mol Genet. 1994;3:559–64.

    Article  CAS  Google Scholar 

  35. Golovnina K, Blinov A, Akhmametyeva EM, Omelyanchuk LV, Chang LS. Evolution and origin of merlin, the product of the neurofibromatosis type 2 (NF2) tumor-suppressor gene. BMC Evol Biol. 2005;5:69.

    Article  Google Scholar 

  36. Chishti AH, Kim AC, Marfatia SM, et al. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem Sci. 1998;23:281–2.

    Google Scholar 

  37. Bruder CE, Hirvelä C, Tapia-Paez I, et al. High-resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH. Hum Mol Genet. 2001;10:271–82.

    Google Scholar 

  38. Shimizu T, Seto A, Maita N, et al. Structural basis for neurofibromatosis type 2. J Biol Chem. 2002;277:10332–6.

    Google Scholar 

  39. Jin H, Sperka T, Herrlich P, Morrison H. Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase. Nature. 2006;442:576–9.

    Article  CAS  Google Scholar 

  40. de Vries M, van der Mey AGL, Hogendoorn PCW. Tumor biology of vestibular schwannoma: a review of experimental data on the determinants of tumor genesis and growth characteristics. Otol Neurotol. 2015;36:1128–36.

    Article  Google Scholar 

  41. Ye K. Phosphorylation of merlin regulates its stability and tumor suppressive activity. Cell Adhes Migr. 2007;1:196–8.

    Article  Google Scholar 

  42. Laulajainen M, Muranen T, Nyman TA, Carpén O, Grönholm M. Multistep phosphorylation by oncogenic kinases enhances the degradation of the NF2 tumor suppressor merlin. Neoplasia. 2011;13:643–52.

    Article  CAS  Google Scholar 

  43. Bretscher A, Reczek D, Berryman M. Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci. 1997;110:3011–8.

    Article  CAS  Google Scholar 

  44. Gutmann DH, Haipek CA, Hoang LK. Neurofibromatosis 2 tumor suppressor protein, merlin, forms two functionally important intramolecular associations. J Neurosci Res. 1999;58:706–16.

    Article  CAS  Google Scholar 

  45. Bianchi AB, Mitsunaga SI, Cheng JQ, et al. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci U S A. 1995;92:10854–8.

    Google Scholar 

  46. Bourn D, Evans G, Mason S, et al. Eleven novel mutations in the NF2 tumour suppressor gene. Hum Genet. 1995;95:572–4.

    Google Scholar 

  47. Halliday D, Emmanouil B, Pretorius P, et al. Genetic Severity Score predicts clinical phenotype in NF2. J Med Genet. 2017;54:657–64.

    Google Scholar 

  48. Zhao Y, et al. Intrafamilial correlation of clinical manifestations in neurofibromatosis 2 (NF2). Genet Epidemiol. 2002;23:245–59.

    Article  CAS  Google Scholar 

  49. Zucman-Rossi J, et al. NF2 gene in neurofibromatosis type 2 patients. Hum Mol Genet. 1998;7:2095–101.

    Article  CAS  Google Scholar 

  50. Stamenkovic I, Yu Q. Merlin, a “magic” linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival. Curr Protein Pept Sci. 2010;11:471–84.

    Article  CAS  Google Scholar 

  51. Puliafito A, et al. Collective and single cell behavior in epithelial contact inhibition. Proc Natl Acad Sci. 2012;109:739–44.

    Article  CAS  Google Scholar 

  52. Morrison H, et al. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 2001;15:968–80.

    Article  CAS  Google Scholar 

  53. Pelton PD, et al. Ruffling membrane, stress fiber, cell spreading and proliferation abnormalities in human Schwannoma cells. Oncogene. 1998;17:2195–209.

    Article  CAS  Google Scholar 

  54. Sherman L, et al. Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene. 1997;15:2505–9.

    Article  CAS  Google Scholar 

  55. Tikoo A, Varga M, Ramesh V, Gusella J, Maruta H. An anti-Ras function of neurofibromatosis type 2 gene product (NF2/Merlin). J Biol Chem. 1994;269:23387–90.

    Article  CAS  Google Scholar 

  56. James MF, et al. NF2/Merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol. 2009;29:4250–61.

    Article  CAS  Google Scholar 

  57. Li Y, et al. Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway. Cell Res. 2015;25:801–17.

    Article  CAS  Google Scholar 

  58. Rong R, Tang X, Gutmann DH, Ye K. Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L. Proc Natl Acad Sci U S A. 2004;101:18200–5.

    Article  CAS  Google Scholar 

  59. Jacob A, et al. Phosphatidylinositol 3-kinase/AKT pathway activation in human vestibular schwannoma. Otol Neurotol. 2008;29:58–68.

    Article  Google Scholar 

  60. Welling DB, Packer MD, Chang LS. Molecular studies of vestibular schwannomas: a review. Curr Opin Otol Head Neck Surg. 2007;15:341–6.

    Article  Google Scholar 

  61. The Synodos for NF2 Consortium, Allaway R, Angus SP, Beauchamp RL, Blakeley JO, Bott M, et al. Traditional and systems biology based drug discovery for the rare tumor syndrome neurofibromatosis type 2. PLoS ONE 2018;13(6):e0197350.

    Google Scholar 

  62. Rangwala R, Banine F, Borg JP, Sherman LS. Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between merlin and adherens junction protein complexes in Schwann cells. J Biol Chem. 2005;280:11790–7.

    Article  CAS  Google Scholar 

  63. Morrison H, et al. Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Res. 2007;67:520–7.

    Article  CAS  Google Scholar 

  64. Sainio M, et al. Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. J Cell Sci. 1997;110:2249–60.

    Article  CAS  Google Scholar 

  65. Bai Y, Liu YJ, et al. Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin. Oncogene. 2006;26:836–50.

    Article  Google Scholar 

  66. Shaw RJ, et al. The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Dev Cell. 2001;1:63–72.

    Article  CAS  Google Scholar 

  67. Xiao GH, Chernoff J, Testa JR. NF2: the wizardry of merlin. Genes Chromosomes Cancer. 2003;38:389–99.

    Article  CAS  Google Scholar 

  68. Xiao GH, Beeser A, Chernoff J, Testa JR. p21-activated kinase links Rac/Cdc42 signaling to merlin. J Biol Chem. 2002;277:883–6.

    Article  CAS  Google Scholar 

  69. Kaempchen K. Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells. Hum Mol Genet. 2003;12:1211–21.

    Article  CAS  Google Scholar 

  70. Sixt M. Cell migration: fibroblasts find a new way to get ahead: figure 1. J Cell Biol. 2012;197:347–9.

    Article  CAS  Google Scholar 

  71. Li W, Cooper J, Karajannis MA, Giancotti FG. Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus. EMBO Rep. 2012;13:204–15.

    Article  CAS  Google Scholar 

  72. Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163:811–28.

    Article  CAS  Google Scholar 

  73. Piccolo S, Dupont S, Cordenonsi M. The biology of YAP/TAZ: hippo signaling and beyond. Physiol Rev. 2014;94:1287–312.

    Article  CAS  Google Scholar 

  74. Song H, et al. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci. 2010;107:1431–6.

    Article  CAS  Google Scholar 

  75. Zhang N, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell. 2010;19:27–38.

    Article  CAS  Google Scholar 

  76. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168:960–76.

    Article  CAS  Google Scholar 

  77. Goutagny S. A 4-year phase II study of everolimus in NF2 patients with growing vestibular schwannomas. J Neuro Oncol. 2017;133:443–5.

    Article  CAS  Google Scholar 

  78. Karajannis MA, et al. Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro Oncol. 2013;16:292–7.

    Article  Google Scholar 

  79. Agnihotri S, et al. The genomic landscape of schwannoma. Nat Genet. 2016;48:1339–48.

    Article  CAS  Google Scholar 

  80. Torres-Martín M, et al. Genome-wide methylation analysis in vestibular schwannomas shows putative mechanisms of gene expression modulation and global hypomethylation at the HOX gene cluster. Genes Chromosomes Cancer. 2014;54:197–209.

    Article  Google Scholar 

  81. Mohammad HP, Baylin SB. Linking cell signaling and the epigenetic machinery. Nat Biotechnol. 2010;28:1033–8.

    Article  CAS  Google Scholar 

  82. Hansson CM, et al. Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus. BMC Genomics. 2007;8:16.

    Article  Google Scholar 

  83. Oh JE, et al. Alterations in the NF2/LATS1/LATS2/YAP pathway in schwannomas. J Neuropathol Exp Neurol. 2015;74:952–9.

    Article  CAS  Google Scholar 

  84. Bush ML, et al. AR42, a novel histone deacetylase inhibitor, as a potential therapy for vestibular schwannomas and meningiomas. Neuro Oncol. 2011;13:983–99.

    Article  CAS  Google Scholar 

  85. Jacob A, et al. Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas. Laryngoscope. 2011;122:174–89.

    Article  Google Scholar 

  86. Burns SS, et al. Histone deacetylase inhibitor AR-42 differentially affects cell-cycle transit in meningeal and meningioma cells, potently inhibiting NF2-deficient meningioma growth. Cancer Res. 2013;73:792–803.

    Article  CAS  Google Scholar 

  87. Folkman J. Seminars in medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med. 1995;333:1757–63.

    Article  CAS  Google Scholar 

  88. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.

    Article  CAS  Google Scholar 

  89. Dilwali S, Roberts D, Stankovic KM. Interplay between VEGF-A and cMET signaling in human vestibular schwannomas and schwann cells. Cancer Biol Ther. 2014;16:170–5.

    Article  Google Scholar 

  90. Cayé-Thomasen P, et al. VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate. Otol Neurotol. 2005;26:98–101.

    Article  Google Scholar 

  91. Plotkin SR, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361:358–67.

    Article  CAS  Google Scholar 

  92. Blakeley JO, et al. Efficacy and biomarker study of bevacizumab for hearing loss resulting from neurofibromatosis type 2–associated vestibular schwannomas. J Clin Oncol. 2016;34:1669–75.

    Article  CAS  Google Scholar 

  93. Morris KA, et al. Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation. NOPRAC. 2016;3:281–9.

    Article  Google Scholar 

  94. Liu P, et al. Low-dose bevacizumab induces radiographic regression of vestibular schwannomas in neurofibromatosis type 2: a case report and literature review. Oncol Lett. 2016;11:2981–6.

    Article  CAS  Google Scholar 

  95. Plotkin SR, et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012;33:1046–52.

    Article  Google Scholar 

  96. Fujii M, et al. Convergent signaling in the regulation of connective tissue growth factor in malignant mesothelioma: TGFβ signaling and defects in the Hippo signaling cascade. Cell Cycle. 2014;11:3373–9.

    Article  Google Scholar 

  97. Tanaka K, et al. Therapeutic potential of HSP90 inhibition for neurofibromatosis type 2. Clin Cancer Res. 2013;19:3856–70.

    Article  CAS  Google Scholar 

  98. Ammoun S, Ristic NM, Matthies C, Hilton DA, Hanemann CO. Neurobiology of disease. Neurobiol Dis. 2010;37:141–6.

    Article  CAS  Google Scholar 

  99. Karajannis MA, et al. Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro Oncol. 2012;14:1163–70.

    Article  CAS  Google Scholar 

  100. Ammoun S, Flaiz C, Ristic N, Schuldt J, Hanemann CO. Dissecting and targeting the growth factor-dependent and growth factor-independent sxtracellular signal-regulated kinase pathway in human schwannoma. Cancer Res. 2008;68:5236–45.

    Article  CAS  Google Scholar 

  101. Wong HK, et al. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res. 2010;70:3483–93.

    Article  CAS  Google Scholar 

  102. Beauchamp RL, et al. A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas. Oncotarget. 2015;6:16981–97.

    Article  Google Scholar 

  103. James MF, Stivison E, Beauchamp R, et al. Regulation of mTOR complex 2 signaling in neurofibromatosis 2-deficient target cell types. Mol Cancer Res. 2012;10:649–59.

    Article  CAS  Google Scholar 

  104. Petrilli AM, et al. A chemical biology approach identified PI3K as a potential therapeutic target for neurofibromatosis type 2. Am J Transl Res. 2014;6:471–93.

    Google Scholar 

  105. Ammoun S, et al. The role of insulin-like growth factors signaling in merlin-deficient human schwannomas. Glia. 2012;60:1721–33.

    Article  Google Scholar 

  106. Brastianos PK, et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013;45:285–9.

    Article  CAS  Google Scholar 

  107. Morrow KA, et al. Loss of tumor suppressor merlin results in aberrant activation of Wnt/β-catenin signaling in cancer. Oncotarget. 2016;7:17991–8005.

    Article  Google Scholar 

  108. Clark VE, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013;339:1077–80.

    Article  CAS  Google Scholar 

  109. Koschny R, Boehm C, Sprick MR, et al. Bortezomib sensitizes primary meningioma cells to TRAIL-induced apoptosis by enhancing formation of the death-inducing signaling complex. J Neuropathol Exp Neurol. 2014;73:1034–46.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work performed in this chapter by the authors was supported by the National Institute of Deafness and Communicative Disorders and the Department of Defense Neurofibromatosis Research Program.

Author information

Authors and Affiliations

  1. Massachusetts Eye and Ear, Boston, MA, USA

    Dunia Abdul-Aziz & D. Bradley Welling

  2. Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, USA

    Dunia Abdul-Aziz & D. Bradley Welling

  3. Department of Otolaryngology—Head and Neck Surgery, Department of Otology, Neurotology, and Skull Base Surgery, Department of Audiology, University of Arizona College of Medicine, Tucson, AZ, USA

    Nicholas A. Dewyer

Authors
  1. Dunia Abdul-Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicholas A. Dewyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Bradley Welling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dunia Abdul-Aziz .

Editor information

Editors and Affiliations

  1. Chair of Neurological Surgery, Vice President and Director, The Neurological Institute, University Hospitals of Cleveland, Cleveland, OH, USA

    Nicholas C. Bambakidis

  2. Chief Executive Officer, University Hospitals Health System, Jane and Henry Meyer Distinguished CEO, Endowed Chair, Professor of Otolaryngology Head and Neck Surgery, Professor of Neurological Surgery, Case Western Reserve University, School of Medicine, Cleveland, OH, USA

    Cliff A. Megerian

  3. Emeritus President and CEO, Emeritus Chair, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA

    Robert F. Spetzler

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Abdul-Aziz, D., Dewyer, N.A., Welling, D.B. (2022). Biology and Genetics of Vestibular Schwannomas in Tumors of the Cerebellopontine Angle. In: Bambakidis, N.C., Megerian, C.A., Spetzler, R.F. (eds) Surgery of the Cerebellopontine Angle. Springer, Cham. https://doi.org/10.1007/978-3-031-12507-2_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-12507-2_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-12506-5

  • Online ISBN: 978-3-031-12507-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation