Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas

I. Christiaans, S.B. Kenter, H.C. Brink, T.A.M. van Os, F. Baas, P. van den Munckhof, A.M.J. Kidd, T.J.M. Hulsebos

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Abstract

Background Multiple 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. Results Five 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. Conclusion It 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
Original languageEnglish
Pages (from-to)93-97
JournalJournal of medical genetics
Volume48
Issue number2
DOIs
Publication statusPublished - 2011

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