title: FGFR-TACC gene fusions in human glioma.
abstract: Chromosomal translocations joining in-frame members of the fibroblast growth factor receptor-transforming acidic coiled-coil gene families (the FGFR-TACC gene fusions) were first discovered in human glioblastoma multiforme (GBM) and later in many other cancer types. Here, we review this rapidly expanding field of research and discuss the unique biological and clinical features conferred to isocitrate dehydrogenase wild-type glioma cells by FGFR-TACC fusions. FGFR-TACC fusions generate powerful oncogenes that combine growth-promoting effects with aneuploidy through the activation of as yet unclear intracellular signaling mechanisms. FGFR-TACC fusions appear to be clonal tumor-initiating events that confer strong sensitivity to FGFR tyrosine kinase inhibitors. Screening assays have recently been reported for the accurate identification of FGFR-TACC fusion variants in human cancer, and early clinical data have shown promising effects in cancer patients harboring FGFR-TACC fusions and treated with FGFR inhibitors. Thus, FGFR-TACC gene fusions provide a "low-hanging fruit" model for the validation of precision medicine paradigms in human GBM.
authors.affiliation: Institute for Cancer Genetics, Department of Pediatrics and Pathology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lasorella
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013,Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.affiliation: Institute for Cancer Genetics, Department of Neurology and Pathology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iavarone
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism; D005820:Genetic Testing; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D050596:Oncogene Fusion; D057285:Precision Medicine; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C120584:TACC1 protein, human; D007521:Isocitrate Dehydrogenase; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR-TACC; chromosomal translocations; glioma; personalized therapy