The molecular biology and novel treatments of vestibular schwannomas

A review

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Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin. Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development. Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment. In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1. A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma. Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation. With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

Abbreviations used in this paper: NF1 = neurofibromatosis Type 1; NF2 = NF Type 2.

Article Information

Address correspondence to: Isaac Yang, M.D., Department of Neurological Surgery, University of California, Los Angeles, 695 Charles E. Young Drive South, Gonda 3357, Los Angeles, California 90095-1761. email:

Please include this information when citing this paper: published online July 29, 2011; DOI: 10.3171/2011.6.JNS11131.

© AANS, except where prohibited by US copyright law.



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    Schematic of merlin domains. Merlin consists of a FERM component at the N-terminal domain, which is subdivided into subdomains A, B, and C, and a C-terminal end. The N-terminal domain is postulated to be responsible for merlin's role in cell-cell adhesion and signal transduction. Reproduced with permission from Shimizu et al.: J Biol Chem 277:10332–10336, 2002.

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    Theoretical merlin signaling pathway. Merlin stabilizes cadherin interactions at the cell membrane and is inhibited from phosphorylation by cadherin binding (contact-inhibition). Accumulation of dephosphorylated merlin has an inhibitory function on the Rac pathway, further inhibiting mitogenic signaling. Once merlin is no longer bound to cadherin, PAK can phosphorylate merlin and remove the inhibition on the Rac pathway, which allows for mitogenic signaling. Reproduced with permission from Okada et al.: J Cell Biol 171:361–371, 2005.



Abe TIzumiyama HImaizumi YKobayashi SShimazu MSasaki K: Staged resection of large hypervascular vestibular schwannomas in young adults. Skull Base 11:1992062001


Agrawal YClark JHLimb CJNiparko JKFrancis HW: Predictors of vestibular schwannoma growth and clinical implications. Otol Neurotol 31:8078122010


Ahmad ZBrown CMPatel AKRyan AFOngkeko RDoherty JK: Merlin knockdown in human Schwann cells: clues to vestibular schwannoma tumorigenesis. Otol Neurotol 31:4604662010


Ammoun SCunliffe CHAllen JCChiriboga LGiancotti FGZagzag D: ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma. Neuro Oncol 12:8348432010


An MMZou ZShen HLiu PChen MLCao YB: Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated metaanalysis. Eur J Clin Pharmacol 66:8138212010


Baek SYKim SU: Proliferation of human Schwann cells induced by neu differentiation factor isoforms. Dev Neurosci 20:5125171998


Bai YLiu YJWang HXu YStamenkovic IYu Q: Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin. Oncogene 26:8368502007


Bari MEForster DMKemeny AAWalton LHardy DAnderson JR: Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature. Br J Neurosurg 16:2842892002


Battaglia AMastrodimos BCueva R: Comparison of growth patterns of acoustic neuromas with and without radiosurgery. Otol Neurotol 27:7057122006


Bernards AGusella JF: The importance of genetic mosaicism in human disease. N Engl J Med 331:144714491994


Bianchi ABHara TRamesh VGao JKlein-Szanto AJMorin F: Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet 6:1851921994


Bosco EENakai YHennigan RFRatner NZheng Y: NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferation. Oncogene 29:254025492010


Bourn DCarter SAMason SGareth DEvans RStrachan T: Germline mutations in the neurofibromatosis type 2 tumour suppressor gene. Hum Mol Genet 3:8138161994


Bretcher AEdwards KFehon R: ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 3:5865992002


Carroll SLMiller MLFrohnert PWKim SSCorbett JA: Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration. J Neurosci 17:164216591997


Cayé-Thomasen PBorup RStangerup SEThomsen JNielsen FC: Deregulated genes in sporadic vestibular schwannomas. Otol Neurotol 31:2562662010


Cayé-Thomasen PWerther KNalla ABøg-Hansen TCNielsen HJStangerup SE: VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate. Otol Neurotol 26:981012005


CBTRUS: Central Brain Tumor Registry of the United States 1997 Annual Report ChicagoCentral Brain Tumor Registry of the United States1998


CBTRUS: Primary Brain Tumors in the United States: Statistical Report 1995–1999 ChicagoCentral Brain Tumor Registry of the United States20022003


Clark JJProvenzano MDiggelmann HRXu NHansen SSHansen MR: The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular schwannoma xenografts in nude mice: a preliminary study. Otol Neurotol 29:8468532008


Cole BKCurto MChan AWMcClatchey AI: Localization to the cortical cytoskeleton is necessary for Nf2/merlin-dependent epidermal growth factor receptor silencing. Mol Cell Biol 28:127412842008


Curto MCole BKLallemand DLiu CHMcClatchey AI: Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J Cell Biol 177:8939032007


Deacon SWBeeser AFukui JARennefahrt UEMyers CChernoff J: An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase. Chem Biol 15:3223312008


Evans DGBirch JMRamsden RTSharif SBaser ME: Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43:2892942006


Evans DGHuson SMDonnai DNeary WBlair VTeare D: A genetic study of type 2 neurofibromatosis in the United Kingdom. I Prevalance, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29:8418461992


Fernandez-Valle CGwynn LWood PMCarbonetto SBunge MB: Anti-beta 1 integrin antibody inhibits Schwann cell myelination. J Neurobiol 25:120712261994


Fernandez-Valle CTang YRicard JRodenas-Ruano ATaylor AHackler E: Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. Nat Genet 31:3543622002


Ferrara NGerber HPLeCouter J: The biology of VEGF and its receptors. Nat Med 9:6696762003


Flaiz CAmmoun SBiebl AHanemann CO: Altered adhesive structures and their relation to RhoGTPase activation in merlin-deficient Schwannoma. Brain Pathol 19:27382009


Flaiz CChernoff JAmmoun SPeterson JRHanemann CO: PAK kinase regulates Rac GTPase and is a potential target in human schwannomas. Exp Neurol 218:1371442009


Flaiz CUtermark TParkinson DBPoetsch AHanemann CO: Impaired intercellular adhesion and immature adherens junctions in merlin-deficient human primary schwannoma cells. Glia 56:5065152008


Fucci MJBuchman CABrackmann DEBerliner KI: Acoustic tumor growth: implications for treatment choices. Am J Otol 20:4954991999


Giovannini MRobanus-Maandag Evan der Valk MNiwa-Kawakita MAbramowski VGoutebroze L: Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev 14:161716302000


Gril BPalmieri DBronder JLHerring JMVega-Valle EFeigenbaum L: Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J Natl Cancer Inst 100:109211032008


Hadfield KDSmith MJUrquhart JEWallace AJBowers NLKing AT: Rates of loss of heterozygosity and mitotic recombination in NF2 schwannomas, sporadic vestibular schwannomas and schwannomatosis schwannomas. Oncogene 29:621662212010


Halliday ALSobel RAMartuza RL: Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2. J Neurosurg 74:2482531991


Hansen MRClark JJGantz BJGoswami PC: Effects of ErbB2 signaling on the response of vestibular schwannoma cells to gamma-irradiation. Laryngoscope 118:102310302008


Hansen MRRoehm PCChatterjee PGreen SH: Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation. Glia 53:5936002006


Herbst RS: Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 59:2 Suppl21262004


Houshmandi SSEmnett RJGiovannini MGutmann DH: The neurofibromatosis 2 protein, merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner. Mol Cell Biol 29:147214862009


Hrecka KGierszewska MSrivastava SKozaczkiewicz LSwanson SKFlorens L: Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A 104:11778117832007


Hughes SCFehon RG: Understanding ERM proteins—the awesome power of genetics finally brought to bear. Curr Opin Cell Biol 19:51562007


Hung GColton JFisher LOppenheimer MFaudoa RSlattery W: Immunohistochemistry study of human vestibular nerve schwannoma differentiation. Glia 38:3633702002


Jääskeläinen JPaetau APyykkö IBlomstedt GPalva TTroupp H: Interface between the facial nerve and large acoustic neurinomas. Immunohistochemical study of the cleavage plane in NF2 and non-NF2 cases. J Neurosurg 80:5415471994


James MFManchanda NGonzalez-Agosti CHartwig JHRamesh V: The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association. Biochem J 356:3773862001


Johnson JRCohen MSridhara RChen YFWilliams GMDuan J: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res 11:641464212005


Kaempchen KMielke KUtermark TLangmesser SHanemann CO: Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells. Hum Mol Genet 12:121112212003


Kissil JLBlakeley JOFerner REHuson SMKalamarides MMautner VF: What's new in neurofibromatosis? Proceedsings from the 2009 NF conference: new frontiers. Am J Med Genet Part A 152A:2692832009


Kissil JLJohnson KCEckman MSJacks T: Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J Biol Chem 277:10394103992002


Kissil JLWilker EWJohnson KCEckman MSYaffe MBJacks T: Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell 12:8418492003


Kluwe LMautner VF: Mosaicism in sporadic neurofibromatosis 2 patients. Hum Mol Genet 7:205120551998


LaJeunesse DRMcCartney BMFehon RG: Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization. J Cell Biol 141:158915991998


Lallemand DCurto MSaotome IGiovannini MMcClatchey AI: NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev 17:109011002003


Lanman THBrackmann DEHitselberger WESubin B: Report of 190 consecutive cases of large acoustic tumors (vestibular schwannoma) removed via the translabyrinthine approach. J Neurosurg 90:6176231999


Laulajainen MMuranen TCarpén OGrönholm M: Protein kinase A-mediated phosphorylation of the NF2 tumor suppressor protein merlin at serine 10 affects the actin cytoskeleton. Oncogene 27:323332432008


Lee DJWestra WHStaecker HLong DNiparko JKSlattery WH III: Clinical and histopathologic features of recurrent vestibular schwannoma (acoustic neuroma) after stereotactic radiosurgery. Otol Neurotol 24:6506602003


Li QNance MRKulikauskas RNyberg KFehon RKarplus P: Self-masking in an intact ERM-merlin protein: an active role for the central apical-helical domain. J Mol Biol 365:144614592007


Li WYou LCooper JSchiavon GPepe-Caprio AZhou L: Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 140:4774902010


Lin NUCarey LALiu MCYounger JCome SEEwend M: Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 26:199319992008


Linskey ME: Stereotactic radiosurgery versus stereotactic radiotherapy for patients with vestibular schwannoma: a Leksell Gamma Knife Society 2000 debate. J Neurosurg 93:Suppl 390952000


Linthicum FH JrBrackmann DE: Bilateral acoustic tumors. A diagnostic and surgical challenge. Arch Otolaryngol 106:7297331980


Louis DNRamesh VGusella JF: Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors. Brain Pathol 5:1631721995


Lu JFBruno REppler SNovotny WLum BGaudreault J: Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol 62:7797862008


MacCollin MRamesh VJacoby LBLouis DNRubio MPPulaski K: Mutational analysis of patients with neurofibromatosis 2. Am J Hum Genet 55:3143201994


Maitra SKulikauskas RMGavilan HFehon RG: The tumor suppressors Merlin and Expanded function cooperatively to modulate receptor endocytosis and signaling. Curr Biol 16:7027092006


Marchionni MAGoodearl ADChen MSBermingham-McDonogh OKirk CHendricks M: Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature 362:3123181993


Maurel PSalzer JL: Axonal regulation of Schwann cell proliferation and survival and the initial events of myelination requires PI 3-kinase activity. J Neurosci 20:463546452000


Mautner VFLindenau MBaser MEHazim WTatagiba MHaase W: The neuroimaging and clinical spectrum of neurofibromatosis 2. Neurosurgery 38:8808861996


Mautner VFNguyen RKutta HFuensterer CBokemeyer CHagel C: Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol 12:14182010


McCall CMMiliani de Marval PLChastain PD IIJackson SCHe YJKotake Y: Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol 28:562156332008


McClatchey AFehon R: Merlin and the ERM proteins--regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol 19:1982062009


McLaughlin MEKruger GMSlocum KLCrowley DMichaud NAHuang J: The Nf2 tumor suppressor regulates cell-cell adhesion during tissue fusion. Proc Natl Acad Sci U S A 104:326132662007


Medina PJGoodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 30:142614472008


Mérel PHoang-Xuan KSanson MMoreau-Aubry ABijlsma EKLazaro C: Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas. Genes Chromosomes Cancer 13:2112161995


Meyer TACanty PAWilkinson EPHansen MRRubinstein JTGantz BJ: Small acoustic neuromas: surgical outcomes versus observation or radiation. Otol Neurotol 27:3803922006


Moffat DAIrving RM: The molecular genetics of vestibular schwannoma. J Laryngol Otol 109:3813841995


Moore MJGoldstein DHamm JFiger AHecht JRGallinger S: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:196019662007


Morrison HSherman LSLegg JBanine FIsacke CHaipek CA: The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev 15:9689802001


Morrison HSperka TManent JGiovannini MPonta HHerlich P: Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the action of Ras and Rac. Cancer Res 67:5205272007


Morrissey TKLevi ADNuijens ASliwkowski MBunge RP: Axon-induced mitogenesis of human Schwann cells involves heregulin and p185erbB2. Proc Natl Acad Sci U S A 92:143114351995


Neff BAWelling DBAkhmametyeva EChang LS: The molecular biology of vestibular schwannomas: dissecting the pathogenic process at the molecular level. Otol Neurotol 27:1972082006


Okada TLopez-Lago MGiancotti FG: Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane. J Cell Biol 171:3613712005


Okada TYou LGiancotti FG: Shedding light on Merlin's wizardry. Trends Cell Biol 17:2222292007


Pearson MAReczek DBretscher AKarplus PA: Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101:2592702000


Pelton PDSherman LSRizvi TAMarchionni MAWood PFriedman RA: Ruffling membrane, stress fiber, cell spreading and proliferation abnormalities in human Schwannoma cells. Oncogene 17:219522091998


Plotkin SRHalpin CMcKenna MJLoeffler JSBatchelor TTBarker FG II: Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol 31:113511432010


Plotkin SRStemmer-Rachamimov AOBarker FG IIHalpin CPadera TPTyrrell A: Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 361:3583672009


Propp JMMcCarthy BJDavis FGPreston-Martin S: Descriptive epidemiology of vestibular schwannomas. Neuro Oncol 8:1112006


Qian XKarpova TSheppard AMMcNally JLowy DR: E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. EMBO J 23:173917482004


Qiu RGChen JMcCormick FSymons M: A role for Rho in Ras transformation. Proc Natl Acad Sci U S A 92:11781117851995


Rouleau GAMerel PLutchman MSanson MZucman JMarineau C: Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:5155211993


Ruttledge MHSarrazin JRangaratnam SPhelan CMTwist EMerel P: Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet 6:1801841994


Sainio MZhao FHeiska LTurunen Oden Bakker MZwarthoff E: Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. J Cell Sci 110:224922601997


Schuknecht HF: Pathology of the Ear ed 2PhiladelphiaLea & Febiger1993


Scoles DRBaser MEPulst SM: A missense mutation in the neurofibromatosis 2 gene occurs in patients with mild and severe phenotypes. Neurology 47:5445461996


Seizinger BRMartuza RLGusella JF: Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature 322:6446471986


Shaw RJPaez JGCurto MYaktine APruitt WMSaotome I: The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Dev Cell 1:63722001


Shimizu TSeto AMaita NHamada KTsukita STsukita S: Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain. J Biol Chem 277:10332103362002


Slattery WH IIIFisher LMIqbal ZOppenhiemer M: Vestibular schwannoma growth rates in neurofibromatosis type 2 natural history consortium subjects. Otol Neurotol 25:8118172004


Solares CAPanizza B: Vestibular schwannoma: an understanding of growth should influence management decisions. Otol Neurotol 29:8298342008


Speck OHughes SCNoren NKKulikauskas RMFehon RG: Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity. Nature 421:83872003


Stangerup SETos MCaye-Thomasen PTos TKlökker MThomsen J: Increasing annual incidence of vestibular schwannoma and age at diagnosis. J Laryngol Otol 118:6226272004


Stangerup SETos MThomsen JCaye-Thomasen P: True incidence of vestibular schwannoma?. Neurosurgery 67:133513402010


Strasnick BGlasscock ME IIIHaynes DMcMenomey SOMinor LB: The natural history of untreated acoustic neuromas. Laryngoscope 104:111511191994


Sughrue MEYeung AHRutkowski MJCheung SWParsa AT: Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics. A review. J Neurosurg 114:3593662009


Takahashi KSasaki TMammoto ATakaishi KKameyama TTsukita S: Direct interaction of the Rho GDP dissociation inhibitor with ezrin/radixin/moesin initiates the activation of the Rho small G protein. J Biol Chem 272:23371233751997


Takahashi KSuzuki K: Density-dependent inhibition of growth involves prevention of EGF receptor activation by E-cadherin-mediated cell-cell adhesion. Exp Cell Res 226:2142221996


Tos MCharabi SThomsen J: Incidence of vestibular schwannomas. Laryngoscope 109:7367401999


Tos MStangerup SECayé-Thomasen PTos TThomsen J: What is the real incidence of vestibular schwannoma?. Arch Otolaryngol Head Neck Surg 130:2162202004


Tos MThomsen J: Epidemiology of acoustic neuromas. J Laryngol Otol 98:6856921984


Tos MThomsen JCharabi S: Incidence of acoustic neuromas. Ear Nose Throat J 71:3913931992


Trofatter JAMacCollin MMRutter JLMurrell JRDuyao MPParry DM: A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:7918001993


Turner CE: Paxillin interactions. J Cell Sci 113:Pt 23413941402000


Twist ECRuttledge MHRousseau MSanson MPapi LMerel P: The neurofibromatosis type 2 gene is inactivated in schwannomas. Hum Mol Genet 3:1471511994


Uesaka TShono TSuzuki SONakamizo ANiiro HMizoguchi M: Expression of VEGF and its receptor genes in intracranial schwannomas. J Neurooncol 83:2592662007


Vadlamudi RAdam LTalukder AMendelsohn JKumar R: Serine phosphorylation of paxillin by heregulin-beta1: role of p38 mitogen activated protein kinase. Oncogene 18:725372641999


Vartanian TGoodearl AViehöver AFischbach G: Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3. J Cell Biol 137:2112201997


von Recklinghausen F: Ueber die multiplen Fibrome der Haut und ihre Beziehung zu den multiplen Neuromen BerlinA. Hirschundel1882


Welling DB: Clinical manifestations of mutations in the neurofibromatosis type 2 gene in vestibular schwannomas (acoustic neuromas). Laryngoscope 108:1781891998


Welling DBGuida MGoll FPearl DKGlasscock MEPappas DG: Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and familial schwannomas. Hum Genet 98:1891931996


Wilkinson JSReid HArmstrong GR: Malignant transformation of a recurrent vestibular schwannoma. J Clin Pathol 57:1091102004


Wishart J: Case of tumours in the skull, dura mater, and brain. Edinburg Med Surg J 18:3933971822


Wong ETBrem S: Taming glioblastoma: targeting angiogenesis. J Clin Oncol 25:470547062007


World Health Organization/National Neurofibromatosis Foundation: Prevention and control of neurofibromatosis: memorandum from a joint WHO/NNFF meeting. Bull World Health Organ 70:1731821992


Yamakami IKobayashi EIwadate YSaeki NYamaura A: Hypervascular vestibular schwannomas. Surg Neurol 57:1051122002


Yeung AHSughrue MEKane AJTihan TCheung SWParsa AT: Radiobiology of vestibular schwannomas: mechanisms of radioresistance and potential targets for therapeutic sensitization. Neurosurg Focus 27:6E22009




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