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Contemporary Molecular Biology of Sporadic Vestibular Schwannomas: A Systematic Review and Clinical Implications.

In light of missing systematic reviews in the literature, the objective of this paper is to present the contemporary knowledge on the molecular biology of vestibular schwannomas (VS), based on a systematic literature search. In addition, current and prospected medical therapy based on molecular biology is addressed. A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search was performed in the Pubmed and Embase databases. The following were the words searched: acoustic neuroma/vestibular schwannoma, molecular biology, gene, and microRNA. Specific inclusion and exclusion criteria were determined prior to search. The systematic search rendered 486 articles, ultimately yielding 69 included articles, whereas 35 were from relevant references. The occurrence of at least one mutation in the merlin gene was reported to range between 54% and 76%, whereas the loss of heterozygosity (LOH) corresponding to chromosome 22 occurs in 25% to 83% of sporadic VS. Global gene expression studies indicate that a number of genes other than merlin are at play. No high-level methylation of the merlin gene has been found. Several miRNAs are deregulated in tumor tissue, among others let-7d, miR-221, and miR-21. The acquired knowledge on molecular biology has led to several clinical implementations. Lack of the tumor suppressor merlin plays a principal role in the development of VS. Existing knowledge on the molecular biology has led to the first attempts of targeted medical treatment to prevent tumor growth. Future research is likely to introduce potential imaging markers with prognostic value and new targets for medical therapy.

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