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What is Acoustic Neuroma?

An acoustic neuroma (or schwannoma) is a benign tumor which manifests itself on the sheath surrounding the eighth cranial nerve, affecting the functions of the inner ear. Because many of the symptoms are also indicative of other less serious ailments, acoustic neuromas are often misdiagnosed or undetected.

If untreated, an acoustic neuroma is life-threatening, making it imperative that individuals with persistent inner-ear problems be evaluated to eliminate the possibility of an acoustic neuroma.

 

 

Acoustic Neuroma
 
Acoustic neuroma is of two forms: sporadic and inherited. Both sporadic and bilateral/hereditary acoustic neuromas are characterized by Schwann cell tumors of the vestibular nerve centered in the internal auditory canal.
 
Sporadic form
 
Ninety-five percent of acoustic neuromas are sporadic. Sporadic acoustic neuroma is unilateral and presents in patients usually in the 5th and 6th decades.  It is likely caused by a mutation in the NF2 gene, however factors giving rise to this mutation are still not clear.
 
Unilateral acoustic neuroma can also develop in a small number (5%) of patients suffering from an inherited disease called neurofibromatosis type 1 (NF 1). NF1 is caused by mutation of the NF1 gene on chromosome 17 and results in neuromas of Schwann cells throughout the body.
 
Inherited form
 
The hereditary form of acoustic neuroma is called Neurofobromatosis Type 2. It is bilateral in nature and diagnosed early in life.
 
 
 
The NF2 gene
 
Both sporadic and inherited acoustic neuromas are believed to occur due to malfunctioning of the gene NF2 on chromosome 22. Normally this gene produces a protein called Merlin (also known as schwannomin) in the schwann cells which cover nerve cells. Merlin acts as a tumor suppressant, controlling the abnormal proliferation of schwann cells which could lead to tumor formation.
 
The mechanism by which the Merlin protein is encoded by the tumor suppressor gene NF2 is still not clear. Studies have shown Merlin exerts an antimitogenic effect by interacting with multiple signaling proteins located at or close to the plasma membrane. Merlin trans-locates into the nucleus and binds to and inhibits the E3 ubiquitin ligase CRL4 (DCAF1). Genetic evidence indicates that inactivation of Merlin induces oncogenic gene expression (i.e. Tumor forming), hyper proliferation, and tumorigenicity by unleashing the activity of CRL4 (DCAF1). In addition to providing a potential explanation for the diverse effects that loss of Merlin exerts in multiple cell types, these findings suggest that compounds inhibiting CRL4 (DCAF1) may display therapeutic efficacy in Neurofibromatosis type 2.
 
 
 
References

Ferri FF. (2011). Ferri’s Clinical Advisor 2011 Instant Diagnosis and Treatment. Philadelphia, PA: Mosby, Inc.
 
Flint PW, Haughey BH, Lund VJ, Niparko JK, Richardson MA, Robbins KT, Thomas JR. (2010). Cummings Otolaryngology - Head and Neck Surgery (5th ed.). Philadelphia, PA: Mosby, Inc.

Rouleau GA, Wertelecki W, Haines JL, Hobbs WJ, Trofatter JA, Seizinger BR, Martuza RL, Superneau DW, Conneally PM, Gusella JF. (1987). Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature. 329(6136):246-8. (http://www.ncbi.nlm.nih.gov/pubmed/2888021) Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B, et al. (1993). Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature. 363(6429):515-21. (http://www.ncbi.nlm.nih.gov/pubmed?term=8379998) Stemmer-Rachamimov AO, Xu L, Gonzalez-Agosti C, Burwick JA, Pinney D, Beauchamp R, Jacoby LB, Gusella JF, Ramesh V, Louis DN. (1997). Universal absence of merlin, but not other ERM family members, in schwannomas. Am J Pathol. 151(6):1649-54. (http://www.ncbi.nlm.nih.gov/pubmed/9403715)
 
Li W, You L, Cooper J, Schiavon G, Pepe-Caprio A, Zhou L, Ishii R, Giovannini M, Hanemann CO, Long SB,  Erdjument-Bromage H, Zhou P, Tempst P, Giancotti FG. (2010). Merlin/NF2 Suppresses Tumorigenesis by Inhibiting the E3 Ubiquitin Ligase CRL4DCAF1 in the Nucleus. Cell 140(4): 477–490. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828953/?tool=pmcentrez)