Hearing loss is the most common symptom in patients with vestibular schwannoma (VS). In the past, compressive mechanisms caused by the tumoral mass and its growth have been regarded as the most likely causes of the hearing loss associated with VS. Interestingly, new evidence proposes molecular mechanisms as an explanation for such hearing loss. Among the molecular mechanisms proposed are methylation of TP73, negative expression of cyclin D1, expression of B7-H1, increased expression of the platelet-derived growth factor A, underexpression of PEX5L, RAD54B, and PSMAL, and overexpression of CEA. Many molecular mechanisms are involved in vestibular schwannoma development; we review some of these mechanisms with special emphasis on hearing loss associated with vestibular schwannoma. 1. Introduction Vestibular schwannomas (VSs) can be classified into two broad groups: unilateral sporadic vestibular schwannoma and those associated with neurofibromatosis type 2 (NF2). VSs constitute 8% of all benign intracranial tumors, and sporadic unilateral schwannomas represent up to 95% of all VSs [1]. As new population-based studies are performed, the true incidence of VS appears to be higher than expected [2–5]. A nationwide study performed in Denmark [2] revealed that the incidence of VS had been rising from 5 cases per million population per year in 1977–1981 to 10 cases in 1992–1995. In 2004, the same research group estimated an incidence of 11.5 cases per million inhabitants per year during a 25-year period (1976–2001) [3]. Data from a US national tumor registry (2010) reported a VS incidence rate of 1.1 cases per 100,000 people per year [4]. On the other hand, Evans et al. found an incidence of 1 case in 80,000 individuals for sporadic VS, and 1 in 70,000 if NF2-related tumors were included [5]. These increasing numbers are probably due to the effect of newer and more sensitive diagnostic tests, especially magnetic resonance imaging (MRI). The age of presentation of VS is usually the fourth and fifth decades. Even though a benign tumor, if large enough, can cause neurological symptoms like hydrocephalus, brainstem compression, herniation, and ultimately death. NF2 is an autosomal dominant disease representing 5% of all VSs. Patients with NF2 are characterized by having bilateral vestibular schwannomas. Half of these patients do not have a family history of the disease [1] and therefore represent new germline mutations. The Manchester criteria for the diagnosis of NF2 have been described elsewhere [6, 7]. These patients can also present other intracranial benign
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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[15]
L. Del Río Arroyo, L. Lassaletta, C. Alfonso, M. J. Sarriá, and J. Gavilán, “Disociación clínica-tama？o tumoral en el neurinoma del acústico: realidad o problema de medida?” Acta Otorrinolaringologica Espanola, vol. 57, no. 8, pp. 345–349, 2006.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[28]
M. Diensthuber, A. Brandis, T. Lenarz, and T. St？ver, “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.
[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.
[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.
[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.
[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.
[33]
S. R. Rogatto and C. Casartelli, “Cytogenetic study of human neurinomas,” Cancer Genetics and Cytogenetics, vol. 41, p. 278, 1989.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[46]
M. Laulajainen, T. Muranen, T. A. Nyman, O. Carpén, and M. Gr？nholm, “Multistep phosphorylation by oncogenic kinases enhances the degradation of the NF2 tumor suppressor merlin,” Neoplasia, vol. 13, no. 7, pp. 643–652, 2011.
[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.
[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.
[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.
[50]
E. Sahai and C. J. Marshall, “RHO-GTPases and cancer,” Nature Reviews Cancer, vol. 2, no. 2, pp. 133–142, 2002.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[76]
K. D. Robertson, “DNA methylation and human disease,” Nature Reviews Genetics, vol. 6, no. 8, pp. 597–610, 2005.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
