title: Mutational analysis of the NF2 gene in sporadic meningiomas by denaturing high-performance liquid chromatography.
abstract: The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of sporadic meningiomas of the nervous system. In order to evaluate the role of the NF2 gene in sporadic meningiomas, we analyzed the entire coding regions of the NF2 gene in a group of 42 sporadic meningiomas: 17 meningothelial, 11 transitional, 11 fibrous, one secretory, one atypical, and one malignant subtype, using denaturing high-performance liquid chromatography (DHPLC) and sequence analysis. Twenty-one mutations were identified in 20 patients with an overall mutation detection rate of 47.6%. The mutations included nine deletions (exons 1, 2, 5, 10, and 12), resulting in a frameshift, four non-sense mutations (exons 1, 2, and 7), four splice errors (exons 4, 5, 7, and 12), two missense mutations (exon 5) and two silent mutations (exon 11). Among these, 14 novel mutations were also identified in the present study. All mutations were noted in the first 12 exons, the region of homology with the ezrin-moesin-radixin protein. Furthermore, an association between NF2 mutations and histologic subtypes were observed; NF2 mutations were more frequent in fibrous meningiomas (8/11, 73%) and transitional meningiomas (6/11, 55%), than in meningothelial variant (5/17, 29%). These results provide evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas as well as indicating a different tumorigenesis of these meningioma variants.
authors.affiliation: Department of Neurosurgery, School of Medicine, Keimyung University, Daegu 700-712, Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Kim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kwon
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Jeon
authors.forename: Eun-Ik
authors.initials: EI
authors.lastname: Son
authors.forename: Sang-Pyo
authors.initials: SP
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D025581:Neurofibromin 2 / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D025581:Neurofibromin 2