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- DOI: 10.1038/ng.2552
- PMID: 23377182
- UKPMCID: 23377182
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Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas
Smith, Miriam J; O'Sullivan, James; Bhaskar, Sanjeev S; Hadfield, Kristen D; Poke, Gemma; Caird, John; Sharif, Saba; Eccles, Diana; Fitzpatrick, David; Rawluk, Daniel; du Plessis, Daniel; Newman, William G; Evans, D Gareth
Nature genetics. 2013;45(3):295-298.
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Full-text held externally
- DOI: 10.1038/ng.2552
- PMID: 23377182
- UKPMCID: 23377182
Abstract
One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology.