FGFR3 has been found to be mutated in up to 64% of cases of bladder cancer; FGFR3 mutations tend to be exclusive of RAS mutations ,TP53 overexpression, TP53 mutation, but not PIK3CA mutations. However, subsets of cases with co-mutations have been described. FGFR3 mutations (including Y373C) are believed to lead to constitutive activation of the receptor and activation of the RAS-MAPK pathway. FGFR3 mutations are often seen in non-muscle invasive bladder cancers and tend to correlate with low stage and grade; however FGFR3 mutations have also been described in muscle-invasive bladder cancer. Targeted therapies with FGFR3 inhibitors have been explored in patients with bladder cancer.

FGFR3 is one of 4 high affinity tyrosine kinase receptors for the fibroblast growth factor family of ligands. On ligand stimulation, FGFR3 undergoes dimerization and tyrosine autophosphorylation, resulting in cell proliferation or differentiation, depending on the cell context, through the mitogen-activated protein kinase (MAPK) and phospholipase Cγ signal transduction pathways. All known mutations are believed to result in ligand-independent activation of the receptor. Germ line mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia. However, somatic mutations of FGFR3 gene are very rare in brain tumors. In some cases, the possibility of FGFR3 variants being germline can not be excluded. Clinical correlation is recommended.

FGFR3 is one of 4 high affinity tyrosine kinase receptors for the fibroblast growth factor family of ligands. On ligand stimulation, FGFR3 undergoes dimerization and tyrosine autophosphorylation, resulting in cell proliferation or differentiation, depending on the cell context, through the mitogen-activated protein kinase (MAPK) and phospholipase Cγ signal transduction pathways. Some FGFR3 mutations are believed to result in ligand-independent activation of the receptor. Somatic mutations of FGFR3 gene are not reported in thymic tumors. However, in some cases, the possibility of FGFR3 variants being germline can not be excluded. Clinical correlation is recommended.

FGFR3 is one of 4 high affinity tyrosine kinase receptors for the fibroblast growth factor family of ligands. On ligand stimulation, FGFR3 undergoes dimerization and tyrosine autophosphorylation, resulting in cell proliferation or differentiation, , through the mitogen-activated protein kinase (MAPK) and phospholipase Cg signal transduction pathways. Some FGFR3 mutations are believed to result in ligand-independent activation of the receptor. However, FGFR3 F384L mutation is not associated with activation of FGFR and, in NIH-3T3 cells, it was demonstrated to be devoid of any transforming activity. In some cases, the possibility of FGFR3 variants being of germline origin, cannot be excluded. The FGFR3 F384L mutation has been reported as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/134404/). Clinical correlation is recommended.

FGFR3 mutations may be associated with response to the multi-targeted tyrosine kinase inhibitor pazopanib.

This gene is a known cancer gene.

This gene is a known cancer gene.

Balversa (erdafitinib) has been FDA approved for treatment of urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations. FGFR3 is a receptor tyrosine kinase in the RAS-MAPK and PI3K-AKT pathways. FGFR3 has been found to be mutated in up to 64% of cases of bladder cancer and 40% of upper urothelial tract (ureter and renal pelvis) urothelial carcinomas. FGFR3 mutations tend to be exclusive of RAS mutations ,TP53 overexpression, TP53 mutation, but not PIK3CA mutations. However, subsets of cases with co-mutations have been described. Gain of function FGFR3 mutations (including FGFR3 R248C and FGFR3 S249C) are believed to lead to constitutive activation of the receptor and activation of the RAS-MAPK pathway. FGFR3 mutations are often seen in non-muscle invasive bladder cancers and tend to correlate with low stage and grade; however, FGFR3 mutations have also been described in muscle-invasive bladder cancer.

FGFR3 amplification may be associated with response to the multitargeted tyrosine kinase inhibitor pazopanib.

FGFR3 is one of four high affinity tyrosine kinase receptors for the fibroblast growth factor family of ligands. On ligand stimulation, FGFR3 undergoes dimerization and tyrosine autophosphorylation, resulting in cell proliferation or differentiation through the mitogen-activated protein kinase (MAPK) and phospholipase Cg signal transduction pathways. Some FGFR3 mutations are believed to result in ligand-independent activation of the receptor. However, FGFR3 F384L mutation is not associated with activation of FGFR and, in NIH-3T3 cells, it was demonstrated to be devoid of any transforming activity. FGFR3 is altered in 2.9% of pancreatic adenocarcinomas. The FGFR3 F384L mutation has been reported as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/134404/). Clinical correlation is recommended.