Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics

Abstract

Vestibular schwannomas (VSs) are benign tumors arising from the sheath of cranial nerve VIII. The pathogenesis underlying most familial and sporadic VSs has been linked to a mutation in a single gene, the neurofibromin 2 (NF2) gene located on chromosome 22, band q11-13.1. In this review, the authors summarized what is known about the epidemiology of NF2 mutations and patients with VSs. The authors also discuss the function of the NF2 gene product, merlin, and describe the known and hypothetical effects of genetic mutations that lead to merlin dysfunction on a broad variety of cellular and histological end points. A better understanding of the molecular pathobiology of VSs may lead to novel therapeutics to augment current modalities of treatment while minimizing morbidity.

Empirical development of improved diagnostic criteria for neurofibromatosis 2

“…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. [31][32][33][34] Most importantly, we have begun to understand the molecular pathogenesis of NF2, 1,[35][36][37] and this is permitting the development of novel therapeutic initiatives. 25,38 -41 Both NF2 and other conditions with which it may be confused clinically are being recognized more frequently, 42 probably because of the availability of high-quality MRI.…”

Prospects and progress of oncolytic viruses for treating peripheral nerve sheath tumors

“…NF2 is an autosomal dominant disease (affects about 1:25000 births) caused by inactivating mutations of the NF2 tumor suppressor gene located on chromosome 22q12, and characterized by the development of nervous system tumors, ocular abnormalities, and skin tumors 20 . The NF2 gene, encoding merlin (moesin-ezrin-radixin-like protein), is also mutated or lost in most sporadic schwannomas 21, 22 . Schwannomas are often asymptomatic, although vestibular schwannomas often lead to hearing loss, and can usually be treated with surgical resection 2, 20 .…”

Novel age-dependent targets in vestibular schwannomas

“…Various types of mutations have been identified, among them single-base substitutions, insertions, and deletions [4]. The NF2 gene product, merlin, functions as a signal transduction pathway regulating cell-to-cell and cell matrix interactions.…”