Transforming fusions of FGFR and TACC genes in human glioblastoma.
Science
; 337(6099): 1231-5, 2012 Sep 07.
Article
en En
| MEDLINE
| ID: mdl-22837387
ABSTRACT
The brain tumor glioblastoma multiforme (GBM) is among the most lethal forms of human cancer. Here, we report that a small subset of GBMs (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes (FGFR1 or FGFR3) to the transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3, respectively. The FGFR-TACC fusion protein displays oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrects the aneuploidy, and oral administration of an FGFR inhibitor prolongs survival of mice harboring intracranial FGFR3-TACC3-initiated glioma. FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Proteínas de Fusión Oncogénica
/
Transformación Celular Neoplásica
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Glioblastoma
/
Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos
/
Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos
/
Proteínas Fetales
/
Proteínas Asociadas a Microtúbulos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Science
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA