Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma.
Nat Genet
; 46(5): 457-461, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24705252
ABSTRACT
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-ß signaling pathway. These mutations represent new targets for therapeutic intervention in this otherwise incurable disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Genoma Humano
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Mutación Missense
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Neoplasias del Tronco Encefálico
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Receptores de Activinas Tipo I
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Glioma
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido