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Genetics Research International
Volume 2012 (2012), Article ID 856157, 10 pages
http://dx.doi.org/10.1155/2012/856157
Review Article

The Molecular Biology of Vestibular Schwannomas and Its Association with Hearing Loss: A Review

1Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, 14269 Ciudad de México, DF, Mexico
2Department of Otolaryngology, “La Paz” University Hospital, 28046 Madrid, Spain
3Unidad de Investigación, Laboratorio Oncogenetica Molecular, “La Paz” University Hospital, 28046 Madrid, Spain
4Department of Pathology, “La Paz” University Hospital, 28046 Madrid, Spain
5Brain Tumor Biology Unit, CIFA, University of Navarra School of Sciences, 31009 Pamplona, Spain

Received 2 June 2011; Revised 8 October 2011; Accepted 3 November 2011

Academic Editor: Ignacio Del Castillo

Copyright © 2012 Erika Celis-Aguilar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. A. Neff, D. B. Welling, E. Akhmametyeva, and L. S. Chang, “The molecular biology of vestibular schwannomas: dissecting the pathogenic process at the molecular level,” Otology and Neurotology, vol. 27, no. 2, pp. 197–208, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. M. F. Howitz, C. Johansen, M. Tos, S. Charabi, and J. H. Olsen, “Incidence of vestibular schwannoma in Denmark, 1977–1995,” American Journal of Otology, vol. 21, no. 5, pp. 690–694, 2000. View at Google Scholar · View at Scopus
  3. M. Tos, S. E. Stangerup, P. Cayé-Thomasen, T. Tos, and J. Thomsen, “What is the real incidence of vestibular schwannoma?” Archives of Otolaryngology, vol. 130, no. 2, pp. 216–220, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. T. J. Gal, J. Shinn, and B. Huang, “Current epidemiology and management trends in acoustic neuroma,” Otolaryngology, vol. 142, no. 5, pp. 677–681, 2010. View at Google Scholar · View at Scopus
  5. D. G. R. Evans, A. Moran, A. King, S. Saeed, N. Gurusinghe, and R. Ramsden, “Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought,” Otology and Neurotology, vol. 26, no. 1, pp. 93–97, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. D. G. R. Evans, S. M. Huson, D. Donnai et al., “A genetic study of type 2 neurofibromatosis in the United Kingdom. II. Guidelines for genetic counselling,” Journal of Medical Genetics, vol. 29, no. 12, pp. 847–852, 1992. View at Google Scholar · View at Scopus
  7. M. E. Baser, J. M. Friedman, A. J. Wallace, R. T. Ramsden, H. Joe, and D. G. R. Evans, “Evaluation of clinical diagnostic criteria for neurofibromatosis 2,” Neurology, vol. 59, no. 11, pp. 1759–1765, 2002. View at Google Scholar · View at Scopus
  8. L. Kluwe, V. Mautner, B. Heinrich et al., “Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas,” Journal of Medical Genetics, vol. 40, no. 2, pp. 109–114, 2003. View at Google Scholar · View at Scopus
  9. G. Rousseau, T. Noguchi, V. Bourdon, H. Sobol, and S. Olschwang, “SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis,” BMC Neurology, vol. 11, article 9, 2011. View at Publisher · View at Google Scholar
  10. T. J. M. Hulsebos, A. S. Plomp, R. A. Wolterman, E. C. Robanus-Maandag, F. Baas, and P. Wesseling, “Germline mutation of INI1/SMARCB1 in familial schwannomatosis,” American Journal of Human Genetics, vol. 80, no. 4, pp. 805–810, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. K. D. Hadfield, W. G. Newman, N. L. Bowers et al., “Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis,” Journal of Medical Genetics, vol. 45, no. 6, pp. 332–339, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Patil, A. Perry, M. MacCollin et al., “Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas,” Brain Pathology, vol. 18, no. 4, pp. 517–519, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. E. M. Stipkovits, J. E. Van Dijk, and K. Graamans, “Profile of hearing in patients with unilateral acoustic neuromas: the importance of the contralateral ear,” American Journal of Otology, vol. 19, no. 6, pp. 834–839, 1998. View at Google Scholar · View at Scopus
  14. K. M. Stankovic, M. M. Mrugala, R. L. Martuza et al., “Genetic determinants of hearing loss associated with vestibular schwannomas,” Otology and Neurotology, vol. 30, no. 5, pp. 661–667, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Del Río Arroyo, L. Lassaletta, C. Alfonso, M. J. Sarriá, and J. Gavilán, “Disociación clínica-tamaño tumoral en el neurinoma del acústico: realidad o problema de medida?” Acta Otorrinolaringologica Espanola, vol. 57, no. 8, pp. 345–349, 2006. View at Google Scholar · View at Scopus
  16. B. Fong, G. Barkhoudarian, P. Pezeshkian, A. T. Parsa, Q. Gopen, and I. Yang, “The molecular biology and novel treatments of vestibular schwannomas: a review,” Journal of Neurosurgery, vol. 115, no. 5, pp. 906–914, 2011. View at Publisher · View at Google Scholar
  17. D. G. R. Evans, “Neurofibromatosis type 2 (NF2): a clinical and molecular review,” Orphanet Journal of Rare Diseases, vol. 4, no. 1, article 16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. R. K. Wolff, K. A. Frazer, R. K. Jackler, M. J. Lanser, L. H. Pitts, and D. R. Cox, “Analysis of chromosome 22 deletions in neurofibromatosis type 2-related tumors,” American Journal of Human Genetics, vol. 51, no. 3, pp. 478–485, 1992. View at Google Scholar · View at Scopus
  19. R. M. Irving, D. A. Moffat, D. G. Hardy et al., “A molecular, clinical, and immunohistochemical study of vestibular schwannoma,” Otolaryngology, vol. 116, no. 4, pp. 426–430, 1997. View at Google Scholar · View at Scopus
  20. K. D. Hadfield, M. J. Smith, J. E. Urquhart et al., “Rates of loss of heterozygosity and mitotic recombination in NF2 schwannomas, sporadic vestibular schwannomas and schwannomatosis schwannomas,” Oncogene, vol. 29, no. 47, pp. 6216–6221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. L. Lassaletta, M. J. Bello, L. Del Río et al., “DNA methylation of multiple genes in vestibular schwannoma: relationship with clinical and radiological findings,” Otology and Neurotology, vol. 27, no. 8, pp. 1180–1185, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Gonzalez-Gomez, M. J. Bello, M. E. Alonso et al., “CpG island methylation in sporadic and neurofibromatis type 2-associated schwannomas,” Clinical Cancer Research, vol. 9, no. 15, pp. 5601–5606, 2003. View at Google Scholar · View at Scopus
  23. P. Cayé-Thomasen, R. Borup, S. E. Stangerup, J. Thomsen, and F. C. Nielsen, “Deregulated genes in sporadic vestibular schwannomas,” Otology and Neurotology, vol. 31, no. 2, pp. 256–266, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. D. J. Archibald, B. A. Neff, S. G. Voss et al., “B7-H1 expression in vestibular schwannomas,” Otology and Neurotology, vol. 31, no. 6, pp. 991–997, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. R. Cardillo, R. Filipo, S. Monini, N. Aliotta, and M. Barbara, “Transforming growth factor-β1 expression in human acoustic neuroma,” American Journal of Otology, vol. 20, no. 1, pp. 65–68, 1999. View at Google Scholar · View at Scopus
  26. K. Niemczyk, F. M. Vaneecloo, M. H. Lecomte et al., “Correlation between Ki-67 index and some clinical aspects of acoustic neuromas (vestibular schwannomas),” Otolaryngology, vol. 123, no. 6, pp. 779–783, 2000. View at Google Scholar · View at Scopus
  27. K. J. Blair, A. Kiang, J. Wang-Rodriguez, M. A. Yu, J. K. Doherty, and W. M. Ongkeko, “EGF and bFGF promote invasion that is modulated by PI3/Akt kinase and erk in vestibular schwannoma,” Otology and Neurotology, vol. 32, pp. 308–314, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Diensthuber, A. Brandis, T. Lenarz, and T. Stöver, “Co-expression of transforming growth factor-β1 and glial cell line-derived neurotrophic factor in vestibular schwannoma,” Otology and Neurotology, vol. 25, no. 3, pp. 359–365, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Cayé-Thomasen, L. Baandrup, G. K. Jacobsen, J. Thomsen, and S. E. Stangerup, “Immunohistochemical demonstration of vascular endothelial growth factor in vestibular schwannomas correlates to tumor growth rate,” Laryngoscope, vol. 113, no. 12, pp. 2129–2134, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. B. F. O'Reilly, A. Kishore, J. A. Crowther, and C. Smith, “Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas,” Otology and Neurotology, vol. 25, no. 5, pp. 791–796, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. J. A. Rey, M. Josefa Bello, J. M. De Campos, M. Elena Kusak, and S. Moreno, “Cytogenetic analysis in human neurinomas,” Cancer Genetics and Cytogenetics, vol. 28, no. 1, pp. 187–188, 1987. View at Google Scholar · View at Scopus
  32. J. R. Teyssier and D. Ferre, “Frequent clonal chromosomal changes in human non-malignant tumors,” International Journal of Cancer, vol. 44, no. 5, pp. 828–832, 1989. View at Publisher · View at Google Scholar · View at Scopus
  33. S. R. Rogatto and C. Casartelli, “Cytogenetic study of human neurinomas,” Cancer Genetics and Cytogenetics, vol. 41, p. 278, 1989. View at Google Scholar
  34. J. Couturier, O. Delattre, M. Kujas et al., “Assessment of chromosome 22 anomalies in neurimomas by combined karyotype and RFLP analyses,” Cancer Genetics and Cytogenetics, vol. 45, no. 1, pp. 55–62, 1990. View at Publisher · View at Google Scholar · View at Scopus
  35. G. Stenman, L. G. Kindblom, M. Johansson, and L. Angervall, “Clonal chromosome abnormalities and in vitro growth characteristics of classical and cellular schwannomas,” Cancer Genetics and Cytogenetics, vol. 57, no. 1, pp. 121–131, 1991. View at Publisher · View at Google Scholar · View at Scopus
  36. M. J. Bello, J. M. De Campos, M. E. Kusak et al., “Clonal chromosome aberrations in neurinomas,” Genes Chromosomes and Cancer, vol. 6, no. 4, pp. 206–211, 1993. View at Google Scholar · View at Scopus
  37. F. Mertens, P. Dal Cin, I. De Wever et al., “Cytogenetic characterization of peripheral nerve sheath tumours: a report of the CHAMP study group,” Journal of Pathology, vol. 190, no. 1, pp. 31–38, 2000. View at Publisher · View at Google Scholar · View at Scopus
  38. C. Warren, L. A. James, R. T. Ramsden et al., “Identification of recurrent regions of chromosome loss and gain in vestibular schwannomas using comparative genomic hybridisation,” Journal of Medical Genetics, vol. 40, no. 11, pp. 802–806, 2003. View at Google Scholar · View at Scopus
  39. J. A. Rey, M. J. Bello, J. M. De Campos et al., “Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches,” Cancer Genetics and Cytogenetics, vol. 66, no. 1, pp. 1–10, 1993. View at Publisher · View at Google Scholar · View at Scopus
  40. C. E. G. Bruder, K. Ichimura, O. Tingby et al., “A group of schwannomas with interstitial deletions on 22q located outside the NF2 locus shows no detectable mutations in the NF2 gene,” Human Genetics, vol. 104, no. 5, pp. 418–424, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. L. G. Bian, Q. F. Sun, W. Tirakotai et al., “Loss of heterozygosity on chromosome 22 in sporadic schwannoma and its relation to the proliferation of tumor cells,” Chinese Medical Journal, vol. 118, no. 18, pp. 1517–1524, 2005. View at Google Scholar · View at Scopus
  42. P. E. Leone, M. J. Bello, M. Mendiola et al., “Allelic status of 1p, 14q, and 22q and NF2 gene mutations in sporadic schwannomas,” International Journal of Molecular Medicine, vol. 1, no. 5, pp. 889–892, 1998. View at Google Scholar · View at Scopus
  43. G. A. Rouleau, P. Merel, M. Lutchman et al., “Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2,” Nature, vol. 363, no. 6429, pp. 515–521, 1993. View at Publisher · View at Google Scholar · View at Scopus
  44. J. A. Trofatter, M. M. MacCollin, J. L. Rutter et al., “A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor,” Cell, vol. 72, no. 5, pp. 791–800, 1993. View at Publisher · View at Google Scholar · View at Scopus
  45. Q. Li, M. R. Nance, R. Kulikauskas et al., “Self-masking in an intact ERM-merlin protein: an active role for the central α-helical domain,” Journal of Molecular Biology, vol. 365, no. 5, pp. 1446–1459, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Laulajainen, T. Muranen, T. A. Nyman, O. Carpén, and M. Grönholm, “Multistep phosphorylation by oncogenic kinases enhances the degradation of the NF2 tumor suppressor merlin,” Neoplasia, vol. 13, no. 7, pp. 643–652, 2011. View at Publisher · View at Google Scholar
  47. A. I. McClatchey and R. G. Fehon, “Merlin and the ERM proteins—regulators of receptor distribution and signaling at the cell cortex,” Trends in Cell Biology, vol. 19, no. 5, pp. 198–206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. W. Li, L. You, J. Cooper et al., “Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4DCAF1 in the nucleus,” Cell, vol. 140, no. 4, pp. 477–490, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Fritz, I. Just, and B. Kaina, “Rho GTPases are over-expressed in human tumors,” International Journal of Cancer, vol. 81, no. 5, pp. 682–687, 1999. View at Google Scholar · View at Scopus
  50. E. Sahai and C. J. Marshall, “RHO-GTPases and cancer,” Nature Reviews Cancer, vol. 2, no. 2, pp. 133–142, 2002. View at Google Scholar · View at Scopus
  51. E. E. Bosco, Y. Nakai, R. F. Hennigan, N. Ratner, and Y. Zheng, “NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferation,” Oncogene, vol. 29, no. 17, pp. 2540–2549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Kaempchen, K. Mielke, T. Utermark, S. Langmesser, and C. O. Hanemann, “Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells,” Human Molecular Genetics, vol. 12, no. 11, pp. 1211–1221, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Yi, E. W. Wilker, M. B. Yaffe, A. Stemmer-Rachamimov, and J. L. Kissil, “Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2,” Cancer Research, vol. 68, no. 19, pp. 7932–7937, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Herrlich, H. Morrison, J. Sleeman et al., “CD44 acts both as a growth- and invasiveness-promoting molecule and as a tumor-suppressing cofactor,” Annals of the New York Academy of Sciences, vol. 910, pp. 106–120, 2000. View at Google Scholar · View at Scopus
  55. D. H. Gutmann, R. T. Geist, H. M. Xu, J. S. Kim, and S. Saporito-Irwin, “Defects in neurofibromatosis 2 protein function can arise at multiple levels,” Human Molecular Genetics, vol. 7, no. 3, pp. 335–345, 1998. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Lutchman and G. A. Rouleau, “The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells,” Cancer Research, vol. 55, no. 11, pp. 2270–2274, 1995. View at Google Scholar · View at Scopus
  57. J. K. Doherty, W. Ongkeko, B. Crawley, A. Andalibi, and A. F. Ryan, “ErbB and Nrg: potential molecular targets for vestibular schwannoma pharmacotherapy,” Otology and Neurotology, vol. 29, no. 1, pp. 50–57, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. M. R. Hansen, P. C. Roehm, P. Chatterjee, and S. H. Green, “Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation,” GLIA, vol. 53, no. 6, pp. 593–600, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Zhan, N. Modi, A. M. Stewart et al., “Regulation of mixed lineage kinase 3 is required for neurofibromatosis-2-mediated growth suppression in human cancer,” Oncogene, vol. 30, no. 7, pp. 781–789, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. D. Bradley Welling, M. Guida, F. Goll et al., “Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and familial schwannomas,” Human Genetics, vol. 98, no. 2, pp. 189–193, 1996. View at Publisher · View at Google Scholar · View at Scopus
  61. D. G. R. Evans, E. R. Maher, and M. E. Baser, “Age related shift in the mutation spectra of germline and somatic NF2 mutations: hypothetical role of DNA repair mechanisms,” Journal of Medical Genetics, vol. 42, no. 8, pp. 630–632, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. R. M. Irving, T. Harada, D. A. Moffat et al., “Somatic neurofibromatosis type 2 gene mutations and growth characteristics in vestibular schwannoma,” American Journal of Otology, vol. 18, no. 6, pp. 754–760, 1997. View at Google Scholar · View at Scopus
  63. M. E. Baser, L. Kuramoto, H. Joe et al., “Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population-based study,” American Journal of Human Genetics, vol. 75, no. 2, pp. 231–239, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. M. E. Baser, L. Kuramoto, R. Woods et al., “The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2,” Journal of Medical Genetics, vol. 42, no. 7, pp. 540–546, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. M. J. Smith, J. E. Higgs, N. L. Bowers et al., “Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset,” Journal of Medical Genetics, vol. 48, no. 4, pp. 261–265, 2011. View at Publisher · View at Google Scholar
  66. S. K. Selvanathan, A. Shenton, R. Ferner et al., “Further genotype—phenotype correlations in neurofibromatosis 2,” Clinical Genetics, vol. 77, no. 2, pp. 163–170, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. D. G. R. Evans, L. Trueman, A. Wallace, S. Collins, and T. Strachan, “Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations,” Journal of Medical Genetics, vol. 35, no. 6, pp. 450–455, 1998. View at Google Scholar · View at Scopus
  68. B. Abo-Dalo, K. Kutsche, V. Mautner, and L. Kluwe, “Large intragenic deletions of the NF2 gene: breakpoints and associated phenotypes,” Genes Chromosomes and Cancer, vol. 49, no. 2, pp. 171–175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. V. F. Mautner, M. E. Baser, and L. Kluwe, “Phenotypic variability in two families with novel splice-site and frameshift NF2 mutations,” Human Genetics, vol. 98, no. 2, pp. 203–206, 1996. View at Publisher · View at Google Scholar · View at Scopus
  70. M. E. Baser, N. K. Ragge, V. M. Riccardi, T. Janus, B. Gantz, and S. M. Pulst, “Phenotypic variability in monozygotic twins with neurofibromatosis 2,” American Journal of Medical Genetics, vol. 64, no. 4, pp. 563–567, 1996. View at Google Scholar · View at Scopus
  71. J. Zucman-Rossi, P. Legoix, H. Der Sarkissian et al., “NF2 gene in neurofibromatosis type 2 patients,” Human Molecular Genetics, vol. 7, no. 13, pp. 2095–2101, 1998. View at Google Scholar · View at Scopus
  72. C. E. G. Bruder, K. Ichimura, E. Blennow et al., “Severe phenotype of neurofibromatosis type 2 in a patient with a 7.4-MB constitutional deletion on chromosome 22: possible localization of a neurofibromatosis type 2 modifier gene?” Genes Chromosomes and Cancer, vol. 25, no. 2, pp. 184–190, 1999. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Kino, H. Takeshima, M. Nakao et al., “Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma,” Genes to Cells, vol. 6, no. 5, pp. 441–454, 2001. View at Publisher · View at Google Scholar · View at Scopus
  74. L. S. Chang, E. M. Akhmametyeva, Y. Wu, L. Zhu, and D. B. Welling, “Multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the complexity of human neurofibromatosis 2 transcripts,” Genomics, vol. 79, no. 1, pp. 63–76, 2001. View at Publisher · View at Google Scholar · View at Scopus
  75. D. B. Welling, E. M. Akhmametyeva, R. L. Daniels et al., “Analysis of the human neurofibromatosis type 2 gene promoter and its expression,” Otolaryngology, vol. 123, no. 4, pp. 413–418, 2000. View at Google Scholar · View at Scopus
  76. K. D. Robertson, “DNA methylation and human disease,” Nature Reviews Genetics, vol. 6, no. 8, pp. 597–610, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. K. Horiguchi, Y. Tomizawa, M. Tosaka et al., “Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21.3 in brain tumors,” Oncogene, vol. 22, no. 49, pp. 7862–7865, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. M. J. Bello, V. Martinez-Glez, C. Franco-Hernandez et al., “DNA methylation pattern in 16 tumor-related genes in schwannomas,” Cancer Genetics and Cytogenetics, vol. 172, no. 1, pp. 84–86, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. Z. K. Ahmad, X. Altuna, J. P. Lopez et al., “p73 expression and function in vestibular schwannoma,” Archives of Otolaryngology, vol. 135, no. 7, pp. 662–669, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. J. Bénard, S. Douc-Rasy, and J. C. Ahomadegbe, “TP53 family members and human cancers,” Human Mutation, vol. 21, no. 3, pp. 182–191, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Allart, H. Martin, C. Detraves, J. Terrasson, D. Caput, and C. Davrinche, “Human cytomegalovirus induces drug resistance and alteration of programmed cell death by accumulation of deltaN-p73alpha,” Journal of Biological Chemistry, vol. 277, no. 32, pp. 29063–29068, 2002. View at Google Scholar · View at Scopus
  82. D. B. Welling, J. M. Lasak, E. Akhmametyeva, B. Ghaheri, and L. S. Chang, “cDNA microarray analysis of vestibular schwannomas,” Otology and Neurotology, vol. 23, no. 5, pp. 736–748, 2002. View at Google Scholar · View at Scopus
  83. V. Martinez-Glez, C. Franco-Hernandez, L. Alvarez et al., “Meningiomas and schwannomas: molecular subgroup classification found by expression arrays,” International Journal of Oncology, vol. 34, no. 2, pp. 493–504, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. J. M. Lasak, D. B. Welling, E. M. Akhmametyeva, M. Salloum, and L. S. Chang, “Retinoblastoma-cyclin-dependent kinase pathway deregulation in vestibular schwannomas,” Laryngoscope, vol. 112, no. 9, pp. 1555–1561, 2002. View at Google Scholar · View at Scopus
  85. L. Lassaletta, M. Patrón, L. Del Río et al., “Cyclin D1 expression and histopathologic features in vestibular schwannomas,” Otology and Neurotology, vol. 28, no. 7, pp. 939–941, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. B. A. Neff, E. Oberstien, M. Lorenz, A. R. Chaudhury, D. B. Welling, and L. S. Chang, “Cyclin D1 and D3 expression in vestibular schwannomas,” Laryngoscope, vol. 116, no. 3, pp. 423–426, 2006. View at Publisher · View at Google Scholar · View at Scopus
  87. T. Hiramoto, T. Nakanishi, T. Sumiyoshi et al., “Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer,” Oncogene, vol. 18, no. 22, pp. 3422–3426, 1999. View at Publisher · View at Google Scholar · View at Scopus
  88. D. N. Louis, A. J. Hamilton, R. A. Sobel, and R. G. Ojemann, “Pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen: a true secretory meningioma. Case report,” Journal of Neurosurgery, vol. 74, no. 1, pp. 129–132, 1991. View at Google Scholar · View at Scopus
  89. J. Zheng and K.K. Yang T. Miller, “Carcinoembryonic antigen-related adhesion molecule 16 interacts with α-tectorin and is mutated in autosomal dominant hearing loss,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 10, pp. 4218–4223, 2011. View at Google Scholar
  90. L. Lassaletta, V. Martínez-Glez, M. Torres-Martín, J. A. Rey, and J. Gavilán, “cDNA microarray expression profile in vestibular schwannoma: correlation with clinical and radiological features,” Cancer Genetics and Cytogenetics, vol. 194, no. 2, pp. 125–127, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. M. L. Rossi, N. R. Jones, M. M. Esiri, L. Havas, N. Nakamura, and H. B. Coakham, “Mononuclear cell infiltrate, HLA-Dr expression and proliferation in 37 acoustic schwannomas,” Histology and Histopathology, vol. 5, no. 4, pp. 427–432, 1990. View at Google Scholar · View at Scopus
  92. N. Rasmussen, K. Bendtzen, J. Thomsen, and M. Tos, “Specific cellular immunity in acoustic neuroma patients,” Otolaryngology, vol. 91, no. 5, pp. 532–536, 1983. View at Google Scholar · View at Scopus
  93. D. Koutsimpelas, T. Stripf, U. R. Heinrich, W. J. Mann, and J. Brieger, “Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics,” Otology and Neurotology, vol. 28, no. 8, pp. 1094–1099, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. P. Cayé-Thomasen, K. Werther, A. Nalla et al., “VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate,” Otology and Neurotology, vol. 26, no. 1, pp. 98–101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. S. R. Plotkin, A. O. Stemmer-Rachamimov, F. G. Barker et al., “Hearing improvement after bevacizumab in patients with neurofibromatosis type 2,” New England Journal of Medicine, vol. 361, no. 4, pp. 358–367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. H. K. Wong, J. Lahdenranta, W. S. Kamoun et al., “Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors,” Cancer Research, vol. 70, no. 9, pp. 3483–3493, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. V. F. Mautner, R. Nguyen, H. Kutta et al., “Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2,” Neuro-Oncology, vol. 12, no. 1, pp. 14–18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. H. K. Wong, J. Lahdenranta, W. S. Kamoun et al., “Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors,” Cancer Research, vol. 70, no. 9, pp. 3483–3493, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. J. L. Kissil, J. O. Blakeley, R. E. Ferner et al., “What's new in neurofibromatosis? Proceedings from the 2009 NF conference: new frontiers,” American Journal of Medical Genetics, Part A, vol. 152, no. 2, pp. 269–283, 2010. View at Publisher · View at Google Scholar · View at Scopus
  100. S. R. Plotkin, C. Halpin, M. J. McKenna, J. S. Loeffler, T. T. Batchelor, and F. G. Barker, “Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients,” Otology and Neurotology, vol. 31, no. 7, pp. 1135–1143, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Ammoun, C. H. Cunliffe, J. C. Allen et al., “ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma,” Neuro-Oncology, vol. 12, no. 8, pp. 834–843, 2010. View at Publisher · View at Google Scholar · View at Scopus