Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas
BackgroundMultiple meningiomas occur in <10% of meningioma patients. Their development may be caused by the presence of a predisposing germline mutation in the neurofibromatosis type 2 (NF2) gene. The predisposing gene in patients with non-NF2 associated multiple meningiomas remains to be identif...
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Published in | Journal of medical genetics Vol. 48; no. 2; pp. 93 - 97 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd
01.02.2011
BMJ Publishing Group BMJ Publishing Group LTD |
Subjects | |
Online Access | Get full text |
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Summary: | BackgroundMultiple meningiomas occur in <10% of meningioma patients. Their development may be caused by the presence of a predisposing germline mutation in the neurofibromatosis type 2 (NF2) gene. The predisposing gene in patients with non-NF2 associated multiple meningiomas remains to be identified. Recently, SMARCB1 was reported to be a potential predisposing gene for multiple meningiomas in a family with schwannomatosis and multiple meningiomas. However, involvement of this gene in the development of the meningiomas was not demonstrated.ResultsFive affected members of a large family with multiple meningiomas were investigated for the presence of mutations in SMARCB1 and NF2. A missense mutation was identified in exon 2 of SMARCB1 as the causative germline mutation predisposing to multiple meningiomas; furthermore, it was demonstrated that, in accordance with the two-hit hypothesis for tumourigenesis, the mutant allele was retained and the wild-type allele lost in all four investigated meningiomas. In addition, independent somatically acquired NF2 mutations were identified in two meningiomas of one patient with concomitant losses of the wild-type NF2 allele.ConclusionIt is concluded that, analogous to the genetic events in a subset of schwannomatosis associated schwannomas, a four-hit mechanism of tumour suppressor gene inactivation, involving SMARCB1 and NF2, might be operative in familial multiple meningiomas associated meningiomas. |
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Bibliography: | PMID:20930055 ark:/67375/NVC-HJLHVRBL-R istex:245DC5BAFD51EDC226DA300903D9A9DBE180D358 ArticleID:jmedgenet82420 href:jmedgenet-48-93.pdf local:jmedgenet;48/2/93 ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0022-2593 1468-6244 1468-6244 |
DOI: | 10.1136/jmg.2010.082420 |