Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. Issue 2 (7th October 2010)

• Record Type: Journal Article
• Authors: Christiaans, I; Kenter, S B; Brink, H C; van Os, T A M; Baas, F; van den Munckhof, P; Kidd, A M J; Hulsebos, T J M
• Is Part Of: Journal of medical genetics. Volume 48:Issue 2(2011)
• Page Start: 93
• Page End: 97
• Publication Date: 2010-10-07
• Subjects: Molecular genetics -- neuro oncology; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2010.082420
• Languages: English
• ISSNs: 1468-6244

Abstract

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.