| Project/Area Number |
11671667
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Tonoku University |
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Principal Investigator |
HASHIMOTO Sho Tohoku Univ., Graduate School of Med., Associate Professor, 大学院・医学系研究科, 助教授 (20156285)
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| Co-Investigator(Kenkyū-buntansha) |
KAKEHATA Seiji Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (90261619)
HORII Akira Tohoku Univ., Graduate School of Med., Professor, 大学院・医学系研究科, 教授 (40249983)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | CGH / FISH / PCR-SSCP / NF2 gene / 2 hit theory / 聴神経腫瘍 / CGH / FISH |
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| Research Abstract |
It has been reported that the NF2 gene on 22q12 was isolated as the responsible gene for NF2. Previous studies have reported that 60% of familial and sporadic schwannomas showed inactivation of the NF2 gene, but genetic alterations of remaining 40% tumors remains elucidative. Moreover, detailed genetic alterations of this tumor remain an open question. In this study, we analyzed genomic alterations in 13 sporadic vestibular schwannomas as well as 4 other schwannomas (1 facial and 3 cervical) using comparative genomic hybridization (CGH). Only loss of chromosome 22q (5/13, 38%) was the notable abnormality. Furthermore, we performed fluorescence in situ hybridization analysis with a genomic BAC clone harboring the NF2 gene and found that the 5 tumors with loss detected by CGH as well as three cases (46%, 6/13) showed loss of the NF2 locus. Mutation search by direct sequencing was also performed and found that 85% (11/13) of the tumors had one or two mutations in the NF2 gene ; 8 (62%) of 13 cases had two inactivating mutations, either a somatic mutation in one allele coupled with loss of the other allele or two independent somatic mutations, in the NF2 gene. Our present results suggested that (i) most of the sporadic vestibular schwannomas have two-hit mutation in the NF2 gene, and (ii) only NF2 is the major causative gene in the genesis of vestibular schwannomas that is activated or inactivated by copy number alterations.
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