DNA Methylation of Multiple Genes in Vestibular Schwannoma

Lassaletta, Luis; Bello, M. Josefa; Rı́o, Laura Del; Alfonso, Carolina; Roda, J.M.; Rey, Juan A.; Gavilán, Javiér

doi:10.1097/01.mao.0000226291.42165.22

Cited by 35 publications

(15 citation statements)

References 25 publications

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“…None of our patients showed repressed expression of the NF2 gene due to hypermethylation of the promoter region. Instead, methylation of other tumor-related genes may have played a role in the development of these vestibular schwannomas [22].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…Presence of a modifier gene [72], methylation of the regulatory region [21, 22, 73], posttranscriptional alternative splicing, and differential polyadenylation of the NF2 gene [74] are proposed as possible causes. On the other hand, the NF2 gene promoter area is a region of DNA that facilitates transcription.…”

Section: Mutations Of the Nf2 Gene Dna Methylation And Hearing Lossmentioning

confidence: 99%

“…It has been claimed that DNA methylation represses transcription directly, by inhibiting the binding of transcription factors, or indirectly, by recruiting methyl-CpG-binding proteins. Hypermethylation of the promoter-associated CpG islands leads to transcriptional silencing and finally to epigenetic inactivation of tumor suppressor genes [21]. The DNA methylation of VS has not been fully studied.…”

Section: Mutations Of the Nf2 Gene Dna Methylation And Hearing Lossmentioning

confidence: 99%

“…The molecular biology of VS has been explained by several pathogenic mechanisms including NF2 gene mutation [1, 16, 17], chromosome 22 loss [16–20], NF2 gene mitotic recombination [18, 20], DNA methylation [21, 22], deregulation of genes [23], immunogenic factors [24, 25], cytokines, and growth factors [26–30]. Early data on the genetic alterations of VS were provided by cytogenetic studies [31–37].…”

Section: Introductionmentioning

confidence: 99%

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

Celis‐Aguilar

Lassaletta

Torres‐Martín

et al. 2012

Genetics Research International

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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.

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“…Elevated frequencies in genes known for their implication in diverse tumor types have been observed: THBS1 (30-36%), TP73 (19-27%), MGMT (16-20%), NF2 (18%), TIMP-3 (18%), RB1/p16INK4a pair (15%) and hMLH1 (21%) [63,64]. A further study has shown a correlation between clinical-radiological features and the aberrant hypermethylation of genic promoters in VS and significant associations of CASP8 with RASSF1A, and between the age of the patient and the tumor grade; also, a relation between the auditory loss and the methylation of TP73 has been observed, as well as an inverse correlation between the hypermethylation of RASSF1A and the clinical grade of tumor growth [65].…”

Section: Molecular Genetics Of Schwannomasmentioning

confidence: 92%

Microarray Gene Expression Profiling in Meningiomas and Schwannomas

Martinez-Glez¹,

Franco-Hernandez²,

Rey

2008

CMC

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Microarray gene expression profiling is a high throughput system recently used in basic and applied research. It provides a large amount of data -at molecular level- that once acquired, must be functionally integrated in order to find common patterns within a defined group of biological samples. In addition to identification of differentially expressed genes and the establishment of gene regulation patterns, microarrays may also allow us to discover new tumor markers that could have a great impact on the improvement of clinical practice and therapeutics for cancer. The classification method used for cancer is currently based on the morphological characteristics of the biological samples. The information obtained with this method is limited, omitting many important tumor characteristics like the proliferation rate, the capacity of invasion and metastases, as well as the possible development of mechanisms of cellular resistance to treatment. Microarrays can be used in combination with conventional diagnostics as a helpful complement. In this review we focus on how this technology has contributed to our knowledge of the molecular pathogenesis of meningiomas and schwannomas, its potential role as a useful tool for tumor classification and its application in clinical practice.

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DNA Methylation of Multiple Genes in Vestibular Schwannoma

Abstract: Aberrant methylation of tumor-related genes may play a role in the development of vestibular schwannomas. Our results may provide useful clues to the development of prognostic assays for these tumors.

Cited by 35 publications

References 25 publications

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

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

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

Microarray Gene Expression Profiling in Meningiomas and Schwannomas

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