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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
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.
1061-4036
295-298
Smith, Miriam J.
cd4a4e1e-96e4-4f04-ac9d-ed5579f75613
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.
cd4a4e1e-96e4-4f04-ac9d-ed5579f75613
O'Sullivan, James
fed9e230-5240-4196-9bca-42ea5b938a3a
Bhaskar, Sanjeev S.
d7ed3a26-efcd-42ea-8c93-5c4fb3b8d992
Hadfield, Kristen D.
7087d730-2947-4615-a08f-f673632d5ead
Poke, Gemma
21a56bd8-058c-4e0e-9cde-367718542aaf
Caird, John
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Sharif, Saba
9e976d1f-c6b2-4278-a2ea-40cc813269ad
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Fitzpatrick, David
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Rawluk, Daniel
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du Plessis, Daniel
f1c56178-c295-44ed-bd4d-0c5338330200
Newman, William G.
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Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c

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), 295-298. (doi:10.1038/ng.2552). (PMID:23377182)

Record type: Article

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

Identifiers

Local EPrints ID: 352317
URI: http://eprints.soton.ac.uk/id/eprint/352317
ISSN: 1061-4036
PURE UUID: eb7a3532-3e9f-4b67-8901-15518b2ae702
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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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: Diana Eccles ORCID iD
Author: David Fitzpatrick
Author: Daniel Rawluk
Author: Daniel du Plessis
Author: William G. Newman
Author: D. Gareth Evans

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