The Molecular Biology of Vestibular Schwannomas: Dissecting the Pathogenic Process at the Molecular Level

Neff, Brian A.; Welling, D. Bradley; Akhmametyeva, Elena M.; Chang, Long-Sheng

doi:10.1097/01.mao.0000180484.24242.54

Cited by 63 publications

(54 citation statements)

References 104 publications

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“…Since 1997, when the most recent set of diagnostic criteria were proposed, the natural history of NF2 has become more clearly defined, 19 -24 and management of the disease has improved. 1,2,25-27 Molecular testing for NF2 mutations has become clinically available, 1,2,26,28,29 and somatic mosaicism has been found to occur in 25-30% of de novo NF2 patients. 11,12 Schwannomatosis has been defined as a distinct clinical entity, 9 excluded from the NF2 locus, 30 and shown to be related to mutations of the SMARCB1 locus in some patients.…”

Section: Discussionmentioning

confidence: 99%

Empirical development of improved diagnostic criteria for neurofibromatosis 2

Baser¹,

Friedman

Joe

et al. 2011

Genetics in Medicine

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Section: Discussionmentioning

confidence: 99%

Empirical development of improved diagnostic criteria for neurofibromatosis 2

Baser¹,

Friedman

Joe

et al. 2011

Genetics in Medicine

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“…Given the heterogeneity of the clinical response to various types of mutations, no clear genotype/phenotype correlation has been established [9]. However, a recent study reported a significant relationship between tumor behavior and genetic alteration in Chinese patients [6].…”

Section: Introductionmentioning

confidence: 99%

Genetic and Epigenetic Alterations of the NF2 Gene in Sporadic Vestibular Schwannomas

et al. 2012

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BackgroundMutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior.Methodology/Principal Findings NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study.Conclusions/SignificanceThe molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth.

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“…50,51 In vitro, treatment of NF2-deficient cells with HER-1/EGFR inhibitors can reduce cellular proliferation. The finding that overexpression of various growth factor receptors in sporadic VS correlate with higher growth rate 26 further spurred efforts to find drug therapies that could be used as molecular targeting agents for these tumors.…”

Section: Current Experience With Targeted Chemotherapymentioning

confidence: 99%