A small subset of glioblastoma multiforme tumors (~3%) are associated with chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor genes FGFR1 or FGFR3 to the C-terminal transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3. Experiments in Drosophila have used a FGFR3-TACC3 (or F3-T3) fusion.
A UAS construct of a human fusion gene, Hsap\FGFR3::Hsap\TACC3, has been introduced into flies. When the fusion gene is been expressed using a glia-specific GAL4 driver, larvae exhibit glial neoplasia with enlargement and malformation of the larval brain lobe and ventral nerve cord; larval lethality results. This system has been used to assess the effects of interacting genes.
[updated Apr. 2019 by FlyBase; FBrf0222196]
Singh et al. (2012, pubmed:22837387) reported that a small subset of glioblastoma multiforme tumors (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. [from MIM:134934, MIM:605303; 2019.04.11]
FGFR3 encodes a member of the fibroblast growth factor receptor (FGFR) family, tyrosine-protein kinases that acts as cell-surface receptors for fibroblast growth factors and play essential roles in the regulation of cell proliferation, differentiation and apoptosis. FGFR family members differ from one another in their ligand affinities and tissue distribution. The FGFR proteins are involved in a wide array of pathways known to play a significant role in cancer. [Gene Cards, FGFR3; 2019.04.11]
The TACC domain identifies a family of centrosomal proteins that can interact with microtubules (Gergely et al., 2000; pubmed:11121038).
TACC3 encodes a motor spindle protein that plays a role in the microtubule-dependent coupling of the nucleus and the centrosome, affecting stabilization of the mitotic spindle.
The FGFR-TACC 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 ameliorates aneuploidy and prolongs survival in a mouse model (Singh et al, 2012; pubmed:22837387).
Many to one: 3 human to 1 Drosophila.
Many to many: multiple genes in both species.
