Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma
Diffuse intrinsic pontine gliomas (DIPGs) are highly infiltrative malignant glial neoplasms of the ventral pons that, due to their location within the brain, are unsuitable for surgical resection and consequently have a universally dismal clinical outcome. The median survival time is 9-12 months, wi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group
2014
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| _version_ | 1797073923046637568 |
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| author | Taylor, K Mackay, A Truffaux, N Butterfield, Y Morozova, O Philippe, C Castel, D Grasso, C Vinci, M Carvalho, D Carcaboso, A de Torres, C Cruz, O Mora, J Entz-Werle, N Ingram, W Monje, M Hargrave, D Bullock, A Puget, S Yip, S Jones, C Grill, J |
| author_facet | Taylor, K Mackay, A Truffaux, N Butterfield, Y Morozova, O Philippe, C Castel, D Grasso, C Vinci, M Carvalho, D Carcaboso, A de Torres, C Cruz, O Mora, J Entz-Werle, N Ingram, W Monje, M Hargrave, D Bullock, A Puget, S Yip, S Jones, C Grill, J |
| author_sort | Taylor, K |
| collection | OXFORD |
| description | Diffuse intrinsic pontine gliomas (DIPGs) are highly infiltrative malignant glial neoplasms of the ventral pons that, due to their location within the brain, are unsuitable for surgical resection and consequently have a universally dismal clinical outcome. The median survival time is 9-12 months, with neither chemotherapeutic nor targeted agents showing substantial survival benefit in clinical trials in children with these tumors. We report the identification of recurrent activating mutations in the ACVR1 gene, which encodes a type I activin receptor serine/threonine kinase, in 21% of DIPG samples. Strikingly, these somatic mutations (encoding p.Arg206His, p.Arg258Gly, p.Gly328Glu, p.Gly328Val, p.Gly328Trp and p.Gly356Asp substitutions) have not been reported previously in cancer but are identical to mutations found in the germ line of individuals with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP) and have been shown to constitutively activate the BMP-TGF-Î 2 signaling pathway. These mutations represent new targets for therapeutic intervention in this otherwise incurable disease. © 2014 Nature America, Inc. All rights reserved. |
| first_indexed | 2024-03-06T23:28:52Z |
| format | Journal article |
| id | oxford-uuid:6b558c54-7321-4012-8df8-75d42d25b914 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:28:52Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:6b558c54-7321-4012-8df8-75d42d25b9142022-03-26T19:03:16ZRecurrent activating ACVR1 mutations in diffuse intrinsic pontine gliomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b558c54-7321-4012-8df8-75d42d25b914EnglishSymplectic Elements at OxfordNature Publishing Group2014Taylor, KMackay, ATruffaux, NButterfield, YMorozova, OPhilippe, CCastel, DGrasso, CVinci, MCarvalho, DCarcaboso, Ade Torres, CCruz, OMora, JEntz-Werle, NIngram, WMonje, MHargrave, DBullock, APuget, SYip, SJones, CGrill, JDiffuse intrinsic pontine gliomas (DIPGs) are highly infiltrative malignant glial neoplasms of the ventral pons that, due to their location within the brain, are unsuitable for surgical resection and consequently have a universally dismal clinical outcome. The median survival time is 9-12 months, with neither chemotherapeutic nor targeted agents showing substantial survival benefit in clinical trials in children with these tumors. We report the identification of recurrent activating mutations in the ACVR1 gene, which encodes a type I activin receptor serine/threonine kinase, in 21% of DIPG samples. Strikingly, these somatic mutations (encoding p.Arg206His, p.Arg258Gly, p.Gly328Glu, p.Gly328Val, p.Gly328Trp and p.Gly356Asp substitutions) have not been reported previously in cancer but are identical to mutations found in the germ line of individuals with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP) and have been shown to constitutively activate the BMP-TGF-Î 2 signaling pathway. These mutations represent new targets for therapeutic intervention in this otherwise incurable disease. © 2014 Nature America, Inc. All rights reserved. |
| spellingShingle | Taylor, K Mackay, A Truffaux, N Butterfield, Y Morozova, O Philippe, C Castel, D Grasso, C Vinci, M Carvalho, D Carcaboso, A de Torres, C Cruz, O Mora, J Entz-Werle, N Ingram, W Monje, M Hargrave, D Bullock, A Puget, S Yip, S Jones, C Grill, J Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| title | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| title_full | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| title_fullStr | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| title_full_unstemmed | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| title_short | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| title_sort | recurrent activating acvr1 mutations in diffuse intrinsic pontine glioma |
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