Molecular genetics alterations and tumor behavior of sporadic vestibular schwannoma from the People's Republic of China

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. Four highly polymorphic microsatellite DNA markers were used to observe the frequency of loss of heterozygosity (LOH) i...

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Bibliographic Details
Published in:Journal of neuro-oncology 2005-07, Vol.73 (3), p.253-260
Main Authors: BIAN, Liu-Guan, TIRAKOTAI, Wuttipong, SUN, Qing-Fang, ZHAO, Wei-Guo, SHEN, Jian-Kang, LUO, Qi-Zhong
Format: Article
Language:English
Subjects:
Adult
Aged
Base Sequence
Biological and medical sciences
Blotting, Western
China
Chromosomes, Human, Pair 22 - genetics
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
DNA Mutational Analysis
Female
Genes, Neurofibromatosis 2
Humans
Immunohistochemistry
Loss of Heterozygosity
Male
Medical sciences
Microsatellite Repeats
Middle Aged
Mutation
Neurofibromin 2 - metabolism
Neurology
Neuroma, Acoustic - genetics
Neuroma, Acoustic - metabolism
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Tumors of the nervous system. Phacomatoses
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Summary: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. 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. 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. 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.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-004-5176-3