Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Science. 2012 Sep 7;337(6099):1231-5. doi: 10.1126/science.1220834. Epub 2012 Jul 26.

Transforming fusions of FGFR and TACC genes in human glioblastoma.

Author information

  • 1Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.

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.

Comment in

PMID:
22837387
[PubMed - indexed for MEDLINE]
PMCID:
PMC3677224
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk