WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
FGFR3
  • Information
  • View History
  • Pending Review
Interpretation 2247
Tier 1
FGFR3
Variants
FGFR3 R248C
FGFR3 S249C
Primary Sites
Kidney
Ureter
Bladder
Tumor Types
Urothelial Carcinoma
Interpretation

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.

Citations
  1. Kompier LC, et al. (2010) FGFR3, HRAS, KRAS, NRAS and PIK3CA Mutations in Bladder Cancer and Their Potential as Biomarkers for Surveillance and Therapy. PLoS ONE 5(11): e13821.
  2. Chell V, et al. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene. 2013 Jun 20;32(25):3059-70
  3. Ronchetti D, et al. Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations. Oncogene. 2001 Jun 14;20(27):3553-62. PubMed PMID: 11429702.
  4. Lyle SR, Hsieh C-C, Fernandez CA, Shuber AP. Molecular grading of tumors of the upper urothelial tract using FGFR3 mutation status identifies patients with favorable prognosis. Research and Reports in Urology. 2012;4:65-69. doi:10.2147/RRU.S37355.
Last updated: 2020-06-02 01:52:12 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use