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

Abstract

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.

Gamma Knife Radiosurgery does not alter the copy number aberration profile in sporadic vestibular schwannoma

“…To understand the mechanism, we wanted to evaluate whether there are any genetic aberrations associated with GKRS treatment resistance. Previous studies on structural changes in the VS genome have identified chromosome 22q loss as the only recurring event, present in 25-83% of VSs [12]. However, previous studies have used techniques with lower resolution.…”

Anticancer properties and mechanism of action of the quassinoid ailanthone

“…In a first study using human vestibular Schwannoma (VS) cells, AIT was found to negatively regulate miR‐21, which is an abundant microRNA, frequently expressed in cancer cells and upregulated in VS cells (Sass & Cayé‐Thomasen, 2018). It functions as an oncogene, acting as the regulator of programmed cell death 4 (PDCD4) by targeting its 3′‐untranslated region to promote tumor proliferation, migration, and invasion in different types of carcinoma (Zhao et al, 2019).…”

Surgery of the lateral skull base: a 50-year endeavour

“…Merlin gene silencing is a molecular feature shared by unilateral sporadic vestibular schwannomas and bilateral vestibular schwannomas associated with NF2. In sporadic cases, somatic bi-allelic merlin gene inactivation seems essential to tumor formation 9 . Merlin gene mutations consist of insertions, deletions, and single-base substitutions resulting in frameshifts and nonsense mutations.…”

“…Merlin gene mutations consist of insertions, deletions, and single-base substitutions resulting in frameshifts and nonsense mutations. They mainly prompt the synthesis of truncated proteins 910 . NF2 gene inactivation results in total merlin loss, and has been detected in 27% to 61% cases of sporadic vestibular schwannoma 11 .…”

“…Aberrant methylation of the merlin gene promoter regions in schwannomas has been explored as a potential explanation for the lack of functional merlin. Methylation of other genes important to tumor onset, angiogenesis and apoptosis has also been investigated 9 .…”