Immunoblotting analysis of schwannomin/merlin in human schwannomas.
OBJECTIVE
Absent or reduced expression of schwannomin/merlin is associated with tumorigenesis of sporadic schwannomas.


BACKGROUND
The neurofibromatosis type 2 (NF2) gene frequently is mutated in sporadic vestibular schwannomas. The protein product of the NF2 gene is called schwannomin or merlin. Little is known about the mutated forms of schwannomin/merlin present in schwannomas.


METHODS
To investigate further the role of schwannomin/merlin in schwannoma tumorigenesis, immunoblotting experiments were performed. Antischwannomin/merlin-specific antibody that recognizes amino terminus of the protein was used to determine the expression levels of schwannomin/merlin in 16 sporadic vestibular schwannomas, 1 NF2-related vestibular schwannoma, and 5 spinal schwannomas.


RESULTS
The antibody detects a protein of approximately 66 kDa in the Triton X-100-insoluble fraction of tumors. The expression of schwannomin/merlin was severely reduced, <35% of control, in 11 (50%) of 22 sporadic schwannomas and in 1 NF2-related vestibular schwannoma. The intensity of 66-kDa schwannomin/merlin band was moderately reduced, from 35-60%, in 7 (32%) of 22 schwannomas compared to the expression levels found in the human brain. Truncated forms of schwannomin/merlin were identified in three tumors with moderately reduced schwannomin/merlin.


CONCLUSIONS
These results provide new evidence that inactivation of schwannomin/merlin is an important factor in tumorigenesis of sporadic schwannomas.
Harwalkar
J A
JA
Department of Neurosurgery, Cleveland Clinic Foundation, Ohio 44195, USA.
Lee
J H
JH
Hughes
G
G
Kinney
S E
SE
Golubić
M
M
D000328:Adult; D000368:Aged; D002648:Child; D046508:Culture Techniques; D004428:Ear Neoplasms / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D015151:Immunoblotting / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000150:complications / Q000276:immunology*; D016518:Neurofibromatosis 2 / Q000150:complications / Q000175:diagnosis
D007074:Immunoglobulin G