2000年
Tumorigenesis of Meningioma and Vestibular Schwannoma as Evidenced by Molecular Genetics
東海女子大学紀要 = Bulletin of Tokai Women's University
- 巻
- 20
- 号
- 開始ページ
- 191
- 終了ページ
- 210
- 記述言語
- 英語
- 掲載種別
- 出版者・発行元
- 東海女子大学
NF2 is caused by mutations of the NF2 gene. The NF2 gene was mapped to the long arm of chromosome 22 and has recently been isolated. Although meningioma and vestibular schwannoma are usually sporadic tumors, bilateral vestibular schwannoma is a hallmark feature of NF2 and meningioma also occurs frequently in NF2 patients.In this paper, the basics of some fields of molecular genetics were first reviewed, and then, the results of the investigations which the author has conducted on meningioma and vestibular schwannoma were presented. For meningioma study, 23 sporadic meningiomas, 3 hemangioblastomas and one hemangiopericytoma were investigated. For vestibular schwannoma study, 91 sporadic vestibular schwannomas, 2 vestibular schwannomas from NF2 patients and one vagal neurinoma (histologically identical to vestibular schwannoma) were investigated. Paired DNA samples were extracted from the blood and tumor of the patients and analyzed for chromosome 22 LOH. The presence of mutations was screened for in all 17 exons of the NF2 gene by SSCP, and PCR products showing aberrant SSCP bands were subsequently sequenced by conventional DNA sequencing method. Fourteen (61%) of 23 meningiomas showed chromosome 22 LOH and 8 meningiomas (35%) showed somatic NF2 gene mutations. No abnormality was detected in hemangioblastoma and hemangiopericytoma. In vestibular schwannoma study, chromosome 22 LOH was observed in 35 (40%) of 87 cases available for the study, and NF2 gene mutational analysis revealed 40 mutations in 36 tumors (38%). The total number of the cases in which either chromosome 22 LOH or NF2 gene mutation was identified amounted to 52 (55%).The results of the study have confirmed the hypothesis that both meningioma and vestibular schwannoma share a common molecular genetic basis of tumorigenesis. In both tumors, the NF2 gene acts as a tumor suppressor gene and the mechanism of the tumorigenesis is consistent with the "two hit" mutation model of Knudson. The inactivation of the NF2 gene is important in the pathogenesis of not only NF2-related tumors but also in sporadic meningioma and vestibular schwannoma.(Note : The molecular genetic investigations described in this paper were conducted at the Molecular Genetics Laboratory of Addenbrooke's Hospital in Cambridge. U.K. The author expresses his deep appreciation particularly to Mr. Richard M Irving and also to all the members of the Lab for their kind helps.)
- リンク情報
- ID情報
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- ISSN : 0287-0525
- CiNii Articles ID : 110001219137
- CiNii Books ID : AN00260097