Molecular genetics alterations and tumor behavior of sporadic vestibular schwannoma from the People's Republic of China.
OBJECTIVE
To analyze the molecular genetic alteration of sporadic vestibular schwannomas from the People's Republic of China and to correlate these alterations with the tumor behaviors.


METHODS
Four highly polymorphic microsatellite DNA markers were used to observe the frequency of loss of heterozygosity (LOH) in chromosome 22. The NF2 gene mutations were detected by Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The schwannomin/merlin (S/M) expression was examined using anti-NF2 (A-19) IgG under immunohistochemistry and western blot. The proliferative index (LI) of vestibular schwannoma was evaluated by proliferative cell nuclear antigen investigation.


RESULTS
Sixteen vestibular schwannomas (44.4%) showed allele loss. We found 22 mutations in 36 schwannomas. The LI and the growth rate of schwannomas with LOH or mutation were significantly higher than those without LOH or mutation. All of these vestibular schwannomas showed no immunoreaction to anti-NF2(A-19) IgG by immunohistochemistry. By immunoblotting technique, reduced expression of S/M was found in 31 cases (86%). The growth index of schwannomas with severely reduced expression of S/M was significantly higher than those with moderately reduced or normal expression.


CONCLUSIONS
The molecular genetic changes in sporadic vestibular schwannomas from Chinese patients were similar to the previous reports. We demonstrate the relationship between tumor behaviors and genetic alteration (including LOH and mutation of NF2 gene). We propose that inactivation of S/M, may be an important step in tumorigenesis of sporadic vestibular schwannoma.
Department of Neurosurgery, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai, The People's Republic of China. rj11118@yahoo.com
Liu-Guan
LG
Bian
Wuttipong
W
Tirakotai
Qing-Fang
QF
Sun
Wei-Guo
WG
Zhao
Jian-Kang
JK
Shen
Qi-Zhong
QZ
Luo
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D002681:China; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D025581:Neurofibromin 2 / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D025581:Neurofibromin 2