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Exon scanning for mutations of the nf 2 gene in pediatric ependymomas, rhabdoid tumors and meningiomas
Author(s) -
Slavc Irene,
Maccollin Mia M.,
Dunn Michael,
Jones Susan,
Sutton Leslie,
Gusella James F.,
Biegel Jaclyn A.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910640406
Subject(s) - exon , biology , single strand conformation polymorphism , chromosome 22 , locus (genetics) , meningioma , germ cell tumors , carcinogenesis , tumor suppressor gene , neurofibromatosis type 2 , gene mutation , neurofibromatosis , somatic cell , germline mutation , cancer research , genetics , gene , pathology , microbiology and biotechnology , mutation , chromosome , medicine , chemotherapy
Deletions of chromosome 22 have been identified in 3 types of childhood primary brain tumor: meningiomas, rhabdoid or atypical teratoid tumors (ATT) and ependymomas. This implicates the involvement of tumor suppressor genes on chromosome 22 in the genesis of these rare tumors. One such candidate tumor suppressor gene is the recently cloned neurofibromatosis 2 ( NF 2) locus. The purpose of our study was to determine the frequency of germ‐line and somatic NF 2 mutations in a selected group of brain tumors in children. Using single‐strand conformation polymorphism (SSCP) assays we screened 17 exons of the NF 2 gene in 13 pediatric brain tumors and 9 matched normal blood DNA samples. Tumors included 3 meningiomas, 2 rhabdoid or ATTs, 7 ependymomas and 1 malignant tumor of glial lineage. In addition, lymphoblastoid cell lines from 3 patients with rhabdoid/ATT in whom no tumor tissue was available were analyzed for germ‐line mutations. Migration shifts were not detected in any of the normal DNA samples analyzed. Of the 13 tumors screened by SSCP, 1 meningioma with monosomy 22 produced a migration shift in exon 13. DNA sequencing of exon 13 revealed a deletion of a single guanine nucleotide (base 1397) in codon 466, causing a frame shift. While not all mutations might have been picked up by this technique, the data suggest that, similar to adult sporadic meningiomas, some pediatric meningiomas may result from somatic mutations in the NF 2 gene. For rhabdoid tumors and ependymomas it appears that a locus distinct from NF 2 might be responsible for tumorigenesis. © 1995 Wiley‐Liss, Inc.