FGFR1 Gene

FGFR1 gene (FGFR is the acronym for "Fibroblast Growth Factor Receptor") is a protein-coding gene that encodes the fibroblast growth factor receptor. It is located on chromosome 8p11.23. The protein encoded by this gene belongs to the fibroblast growth factor receptor (FGFR) family. The members of the FGFR family differ from each other in their ligand affinity and tissue distribution.

The encoded FGFR1 protein is a member of the fibroblast growth factor family, which consists of 4 receptors and 18 ligands. FGFR1 signaling occurs mainly through PI3K and MAPK signaling pathways.

A representative full-length protein consists of an extracellular region composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain.

The extracellular portion of the protein interacts with fibroblast growth factors (FGF) and initiates a cascade of downstream signals that ultimately influence mitogenesis and differentiation. FGFR1 binds both acidic and basic fibroblast growth factors and is involved in limb induction.

Mutations in the FGFR1 gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome.

Furthermore, chromosomal aberrations involving this gene are associated with myeloproliferative stem cell disorder andstem cell leukemia lymphoma syndrome. Involvement of FGFR1 in tumor diseases are likely. Hereby, auto- and paracrine activation, amplifications and overexpressions play a role.

Evidence suggests amplifications of the FGFR1 gene in lung cancer. They represent a treatment option. However, FGFR1 amplification does not always correlate with protein expression.

Mutations of FGFR1 seem to be less frequent but have been described in glioblastomas, pilocytic astrocytomas and Ewing sarcomas.

1. Drago JZ et al (2019) FGFR1 Amplification Mediates Endocrine Resistance but Retains TORC Sensitivity in Metastatic Hormone Receptor-Positive (HR+) Breast Cancer. Clin Cancer Res 25:6443-6451.
2. Trarbach EB et al (2006) Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. J Clin Endocrinol Metab 91:4006-4012
3. Pitteloud N et al (2006) Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol Cell Endocrinol 254-255:60-69.