Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM et al.. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 75: 826

Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown.
Cell (Impact Factor: 32.24). 04/1993; 72(5):791-800. DOI: 10.1016/0092-8674(93)90406-G
Source: PubMed


Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral vestibular schwannomas and other central nervous system tumors including multiple meningiomas. Genetic linkage studies and investigations of both sporadic and familial tumors suggest that NF2 is caused by inactivation of a tumor suppressor gene in chromosome 22q12. We have identified a candidate gene for the NF2 tumor suppressor that has suffered nonoverlapping deletions in DNA from two independent NF2 families and alterations in meningiomas from two unrelated NF2 patients. The candidate gene encodes a 587 amino acid protein with striking similarity to several members of a family of proteins proposed to link cytoskeletal components with proteins in the cell membrane. The NF2 gene may therefore constitute a novel class of tumor suppressor gene.

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Available from: Volker H Haase, Aug 18, 2015
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    • "About 5% of VS cases are bilateral VS that occurs in neurofibromatosis 2 (NF2), an autosomal dominant genetic disease. The NF2 tumor suppressor gene, which was isolated in 1993 [3] [4], was inactivated in both NF2-associated VS and USVS [5]. The growth rates of USVS are highly variable, ranging from slow (0.2 mm diameter/year), to medium (2 mm/year), and to fast (10 mm/year) [6]. "

    Full-text · Article · Jan 2015 · World Journal of Neuroscience
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    • "The NF2 gene is located on chromosome 22q and encodes a 595-amino-acid tumor suppressor protein called either merlin or schwannomin [119, 120] (Figure 5(a)). The predicted merlin protein sequence reveals three structural domains, including an amino terminal FERM (four-point one, ezrin, radixin, and moesin) domain (residues 1–302), a central alpha helical region (residues 303–479), and a carboxyl terminus region (480–595). "
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    ABSTRACT: Development is a tightly regulated process that involves stem cell self-renewal, differentiation, cell-to-cell communication, apoptosis, and blood vessel formation. These coordinated processes ensure that tissues maintain a size and architecture that is appropriate for normal tissue function. As such, tumors arise when cells acquire genetic mutations that allow them to escape the normal growth constraints. In this regard, the study of tumor predisposition syndromes affords a unique platform to better understand normal development and the process by which normal cells transform into cancers. Herein, we review the processes governing normal brain development, discuss how brain cancer represents a disruption of these normal processes, and highlight insights into both normal development and cancer made possible by the study of tumor predisposition syndromes.
    Full-text · Article · Aug 2014
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    • "The human NF2 gene on Chromosome 22q12.2 comprises 17 exons that encode for the 595 amino acid protein merlin; also known as schwannomin [11,12]. This actin-binding protein belongs to the ezrin–radixin–moesin (ERM) family of proteins that organizes and links membrane proteins to the cortical cytoskeleton [13]. "
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    ABSTRACT: Mutagenic loss of the NF2 tumor suppressor gene encoded protein merlin is known to provoke the hereditary neoplasia syndrome, Neurofibromatosis type 2 (NF2). In addition to glial cell-derived tumors in the PNS and CNS, disease-related lesions also affect the skin and the eyes. Furthermore, 60 % of NF2 patients suffer from peripheral nerve damage, clinically referred to as peripheral neuropathy. Strikingly, NF2-associated neuropathy often occurs in the absence of nerve damaging tumors, suggesting tumor-independent events. Recent findings indicate an important role of merlin in neuronal cell types concerning neuromorphogenesis, axon structure maintenance and communication between axons and Schwann cells. In this review, we compile clinical and experimental evidences for the underestimated role of the tumor suppressor merlin in the neuronal compartment.
    Full-text · Article · Jul 2014
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