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.
Description
Transforming fusions of FGFR and TACC genes in human glioblastoma. - PubMed - NCBI
%0 Journal Article
%1 Singh:2012:Science:22837387
%A Singh, D
%A Chan, J M
%A Zoppoli, P
%A Niola, F
%A Sullivan, R
%A Castano, A
%A Liu, E M
%A Reichel, J
%A Porrati, P
%A Pellegatta, S
%A Qiu, K
%A Gao, Z
%A Ceccarelli, M
%A Riccardi, R
%A Brat, D J
%A Guha, A
%A Aldape, K
%A Golfinos, J G
%A Zagzag, D
%A Mikkelsen, T
%A Finocchiaro, G
%A Lasorella, A
%A Rabadan, R
%A Iavarone, A
%D 2012
%J Science
%K cancer-research fulltext gene-fusion rna-seq shouldread
%N 6099
%P 1231-1235
%R 10.1126/science.1220834
%T Transforming fusions of FGFR and TACC genes in human glioblastoma
%U https://www.ncbi.nlm.nih.gov/pubmed/22837387
%V 337
%X 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.
@article{Singh:2012:Science: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.},
added-at = {2018-12-19T14:01:46.000+0100},
author = {Singh, D and Chan, J M and Zoppoli, P and Niola, F and Sullivan, R and Castano, A and Liu, E M and Reichel, J and Porrati, P and Pellegatta, S and Qiu, K and Gao, Z and Ceccarelli, M and Riccardi, R and Brat, D J and Guha, A and Aldape, K and Golfinos, J G and Zagzag, D and Mikkelsen, T and Finocchiaro, G and Lasorella, A and Rabadan, R and Iavarone, A},
biburl = {https://www.bibsonomy.org/bibtex/232a1a9ca2bfae5f286c9d2276e1e9608/marcsaric},
description = {Transforming fusions of FGFR and TACC genes in human glioblastoma. - PubMed - NCBI},
doi = {10.1126/science.1220834},
interhash = {2a914ee680204569446f233b169158a3},
intrahash = {32a1a9ca2bfae5f286c9d2276e1e9608},
journal = {Science},
keywords = {cancer-research fulltext gene-fusion rna-seq shouldread},
month = sep,
number = 6099,
pages = {1231-1235},
pmid = {22837387},
timestamp = {2018-12-19T14:01:46.000+0100},
title = {Transforming fusions of FGFR and TACC genes in human glioblastoma},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22837387},
volume = 337,
year = 2012
}