Identification of three neurofibromatosis type 2 (NF2) gene mutations in vestibular schwannomas

1996 ◽  
Vol 97 (1) ◽  
Author(s):  
Jes�s Sainz ◽  
Karla Figueroa ◽  
MichaelE. Baser ◽  
Stefan-Matthias Pulst
Keyword(s):  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Nf2 Gene

scholarly journals Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 690
Author(s):  
Suha Bachir ◽  
Sanjit Shah ◽  
Scott Shapiro ◽  
Abigail Koehler ◽  
Abdelkader Mahammedi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Neurofibromatosis Type ◽  
Primary Brain Tumor ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Loss Of Function ◽  
Nf2 Gene ◽  
Proliferation And Apoptosis ◽  
Tumor Types

Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis.

Surgical Management of Vestibular Schwannomas in Neurofibromatosis Type 2

2012 ◽  
Vol 73 (S 02) ◽  
Author(s):  
J. Tysome ◽  
R. MacFarlane ◽  
J. Durie-Gair ◽  
N. Donnelly ◽  
R. Mannion ◽  
...  
Keyword(s):  
Surgical Management ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas

Management of Neurofibromatosis Type 2 Associated Vestibular Schwannomas

2021 ◽  
Vol 9 (2) ◽  
pp. 170-176
Author(s):  
Huan Jia ◽  
Ghizlene Lahlou ◽  
Hao Wu ◽  
Olivier Sterkers ◽  
Michel Kalamarides
Keyword(s):  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas

scholarly journals NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii419-iii419
Author(s):  
Sheetal Phadnis ◽  
Mari Hagiwara ◽  
Anna Yaffe ◽  
Carole Mitchell ◽  
Theodore Nicolaides ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Volumetric Response

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

scholarly journals Short-Term Clinico-Radiographic Response to Super-Selective Intra-Arterial Cerebral Infusion of Bevacizumab for the Treatment of Vestibular Schwannomas in Neurofibromatosis Type 2

2012 ◽  
Vol 18 (2) ◽  
pp. 127-132 ◽  
Author(s):  
H.A. Riina ◽  
J-K. Burkhardt ◽  
A. Santillan ◽  
L. Bassani ◽  
A. Patsalides ◽  
...  
Keyword(s):  
Bowel Perforation ◽  
Wound Dehiscence ◽  
Neurofibromatosis Type ◽  
Chemotherapeutic Agents ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Blood Brain Barrier Disruption ◽  
Systemic Side Effects ◽  
Brain Barrier Disruption

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a prevalence of approximately 1 in 30,000. NF 2 is characterized by bilateral vestibular schwannomas, as well as meningiomas, ependymomas and gliomas. Currently, surgical resection and radiotherapy represent the mainstay of treatment, although new studies suggest a role for certain chemotherapeutic agents. Intravenous administration of Bevacizumab (Avastin, Genetech Pharmaceuticals) has been shown to be active in the treatment of vestibular schwannomas. The IV route of administration, however, carries a risk of known systemic side-effects such as bowel perforation, wound dehiscence and pulmonary embolism. In addition, the percentage of drug that reaches the tumor site may be restricted by the blood tumor barrier. This report describes the super-selective intra-arterial infusion of Bevacizumab following blood brain barrier disruption for the treatment of vestibular schwannomas in three patients with Neurofibromatosis type 2. It represents the first time such a technique has been performed for this disease. Additionally, this method of drug delivery may have important implications in the treatment of patients with vestibular schwannomas associated with Neurofibromatosis type 2.

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