1. Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas.
- Author
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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, and Evans, D Gareth
- Subjects
SPINAL tumors ,MENINGIOMA ,NERVOUS system tumors ,NEUROFIBROMATOSIS ,CANCER genetics ,GENETIC mutation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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