This gene is a known cancer gene.

This gene is a known cancer gene.

Amplification of FGFR1 has been reported in less than 5% of cases of pancreatic adenocarcinoma. Sequence analysis has demonstrated an activating KRAS mutation (exon 2) in all FGFR1-amplified cases according to one study. In vitro studies suggest that proliferation of a cell line with FGFR1 amplification may be inhibited using the FGFR1 inhibitor BGJ398. In the proper clinical context, FGFR1 may represent a potential new therapeutic target in a subset of patients harbouring FGFR1-amplified tumours, however, further study is required.

Amplification of FGFR1 has been reported in approximately 10% of breast cancer and may be associated with adverse outcome according to some reports. It has been reported to be associated with increased expression of FGFR1 and increased activity of downstream growth signaling pathways. Some reports suggest FGFR1 may have a role in regulating response to endocrine therapy. FGFR1 amplification may be a targetable alteration in some clinical settings (PubMed IDs: 20179196, 25400686).

FGFR1 activating mutations may be associated with response to the multitargeted tyrosine kinase inhibitor pazopanib.

FGFR1 amplification is associated with poor survival in patients with resected squamous cell lung cancer. FGRF1 amplification may be associated with sensitivity to the multitargeted tyrosine kinase inhibitor pazopanib.

FGFR1 amplification may be associated with sensitivity to the multitargeted tyrosine kinase inhibitor pazopanib in some tumor types.

The FGFR1 copy number gain is part of a large partial chrom 8 gain. The role of FGFR1 in prostate cancer is under study. FGRF1 amplification may be associated with sensitivity to pazopanib in some tumor types.

FGFR1 is a receptor tyrosine kinase activated upon binding of the FGF ligand, which activates RAS-MAPK and PI3K-AKT pathways. Altered function of FGFR1 in cancer may lead to increased cell proliferation and decreased apoptosis. The most common alteration of FGFR1 in lung adenocarcinoma is amplification and point mutations are rare (1% of cases). FGFR1 T141R does not lie within any known functional domains of the FGFR1 protein. T141R has been identified in sequencing studies, but has not been biochemically characterized and therefore, its effect on protein function is unknown. T141R has been reported as a somatic mutation in one case of lung adenocarcinoma in the literature. The clinicopathologic significance of FGFR1 T141R remains to be further elucidated.

This gene is a known cancer gene.

This gene is a known cancer gene.

The receptor tyrosine kinase FGFR2 is one of four fibroblast growth factor receptors designated FGFR1-4 that activate FGF signaling upon trans-autophosphorylation of the receptor dimers. Some genetic alterations of FGFR2 lead to aberrant activation of FGFR2 signaling cascades due to the creation of autocrine signaling loop or the release of FGFR2 from autoinhibition. Activating mutations, including FGFR2 N549K which lies within the protein kinase domain, have been associated with multiple types of malignancies. FGFR2 mutations are more common in tumors of hepatobiliary origin than other solid tumor locations and are found in about 7% of hepatobiliary adenocarcinomas. Treatments with pan-FGFR inhibitors and FGFR2 inhibitors have inhibited proliferation in some tumor types and are under investigation.

The receptor tyrosine kinase FGFR2 is one of four fibroblast growth factor receptors designated FGFR1-4 that activate FGF signalling upon trans-autophosphorylation of the receptor dimers. Some genetic alterations of FGFR2 lead to aberrant activation of FGFR2 signaling cascades due to the creation of autocrine signaling loop or the release of FGFR2 from autoinhibition. It is known that some FGFR2 gene variations including intronic polymorphisms confer a risk for breast cancer, preferentially for estrogen receptor-positive breast tumors. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5-10% of breast tumors. Somatic missense mutations have also been reported in breast cancer leading to ligand independent activation of FGFR2. In cell line and xenograft experiments, inhibition/knockdown of FGFR2 results in anti-tumour effects, suggesting the oncogenic role of FGFR2, raising the potential of FGFR2 as a target of therapy in FGFR2 driven cancers. The P253R variant in FGFR2 has also been described in some constitutional disorders including craniosynostosis syndromes (eg, Apert syndrome).

The receptor tyrosine kinase FGFR2 is one of four fibroblast growth factor receptors designated FGFR1-4 that activate FGF signalling upon trans-autophosphorylation of the receptor dimers. Some genetic alterations of FGFR2 lead to aberrant activation of FGFR2 signaling cascades due to the creation of autocrine signaling loop or the release of FGFR2 from autoinhibition. About 10-16% of primary endometrial cancers harbor activating mutations in FGFR2. These mutations are more frequent in cancers of endometrioid histological subtype compared with serous or clear-cell subtypes. Gain-of-function mutations in the kinase domain lead to ligand-independent activation of the receptor, whereas mutations in the extracellular ligand-binding domain increase the affinity for fibroblast growth factors (FGFs). Both types of mutations have been shown to be potentially oncogenic in endometrial cancer cell lines. In cell line and xenograft experiments, inhibition/knockdown of FGFR2 results in anti-tumour effects, suggesting the oncogenic role of FGFR2, raising the potential of FGFR2 as a target of therapy in FGFR2 driven cancers. Therefore, FGFR-pathway inhibition remains potentially promising in this patient population.