About this item:

116 Views | 106 Downloads

Author Notes:

To whom correspondence should be addressed. E-mail: al2179@columbia.edu (A.L.); rabadan@dbmi.columbia.edu (R.R.); ai2102@columbia.edu (A.I.)

Three of the authors (A.I., A.L., and R.R.) and Columbia University Medical Center have filed a patent application related to the diagnostic and therapeutic use of FGFR-TACC gene fusions.

Next-generation RNA-sequencing data have been deposited into the Database of Genotypes and Phenotypes (accession no. phs000505.v1.p1).

Subjects:

Research Funding:

This work was supported by National Cancer Institute grants R01CA101644 and R01CA131126 (A.L.), R01CA085628 and R01CA127643 (A.I.), U54 CA121852-05 (R.R.), National Library of Medicine grant 1R01LM010140-01 (R.R.), National Institute of Neurological Disorders and Stroke grant R01NS061776 (A.I.), a grant from Partnership for Cure (R.R., 7-78947), and a grant from The Chemotherapy Foundation (A.I.). P.Z. and F.N. are supported by fellowships from the Italian Ministry of Welfare/Provincia di Benevento. G.F. was supported by grants from the Associazione Italiana per la Ricerca sul Cancro and from the Italian Ministry of Health.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • RECEPTOR TYROSINE KINASE
  • CHROMOSOMAL INSTABILITY
  • SELECTIVE INHIBITOR
  • CANCER
  • ANEUPLOIDY
  • FAMILY
  • DISCOVERY
  • POTENT

Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma

Show all authors Show less authors

Tools:

Journal Title:

Вестник Волгоградского государственног... / Science Journal of Volgograd State University. History. Area Studies. International Relations

Volume:

Volume 337, Number 6099

Publisher:

, Pages 1231-1235

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2012 American Association for the Advancement of Science.

Export to EndNote