Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas
Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas
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.
295-298
Smith, Miriam J.
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O'Sullivan, James
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Bhaskar, Sanjeev S.
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Hadfield, Kristen D.
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Poke, Gemma
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Caird, John
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Sharif, Saba
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Eccles, Diana
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Fitzpatrick, David
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Rawluk, Daniel
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du Plessis, Daniel
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Newman, William G.
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Evans, D. Gareth
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March 2013
Smith, Miriam J.
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O'Sullivan, James
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Bhaskar, Sanjeev S.
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Hadfield, Kristen D.
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Poke, Gemma
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Caird, John
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Sharif, Saba
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Eccles, Diana
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Fitzpatrick, David
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Rawluk, Daniel
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du Plessis, Daniel
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Newman, William G.
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Evans, D. Gareth
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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
(2013)
Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas.
Nature Genetics, 45 (3), .
(doi:10.1038/ng.2552).
(PMID: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.
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Published date: March 2013
Organisations:
Cancer Sciences
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Local EPrints ID: 352317
URI: http://eprints.soton.ac.uk/id/eprint/352317
ISSN: 1061-4036
PURE UUID: eb7a3532-3e9f-4b67-8901-15518b2ae702
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Date deposited: 09 May 2013 13:30
Last modified: 15 Mar 2024 02:40
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Contributors
Author:
Miriam J. Smith
Author:
James O'Sullivan
Author:
Sanjeev S. Bhaskar
Author:
Kristen D. Hadfield
Author:
Gemma Poke
Author:
John Caird
Author:
Saba Sharif
Author:
David Fitzpatrick
Author:
Daniel Rawluk
Author:
Daniel du Plessis
Author:
William G. Newman
Author:
D. Gareth Evans
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