FGFR1

Overview

FGFR1 encodes fibroblast growth factor receptor 1, a receptor tyrosine kinase involved in cell proliferation, differentiation, and survival. FGFR1 amplification is enriched in radiation-associated osteosarcoma compared to sporadic osteosarcoma.

Alterations observed in the corpus

  • Amplification in 17% of RT-OS vs 7% of sporadic OS; enriched in the radiation-associated setting PMID:37350195.
  • FGFR1 is a driver event in a subset of fusion-negative rhabdomyosarcoma (FN-RMS) alongside NF1 PMID:37730754.
  • FGFR1 expression regulated by promoter methylation; elevated in bone metastases in prostate cancer PDX models; a novel downstream signature (NRP2, LRP4, TGFBI) was defined PMID:38488813.
  • FGFR1 gain on chromosome 8 identified by whole-genome sequencing of SARC0133 (RMS) in the UCLA sarcoma PDTO biobank (n=194 specimens); the FGFR1 gain correlated with selective PDTO sensitivity to infigratinib (FGFR1/2/3 inhibitor) but not to dovitinib, demonstrating intra-class differentiation within FGFR inhibitors PMID:39305899.
  • FGFR1 appeared in the MSK-CHORD volcano plots of metastasis and Gleason-association analyses across the 24,950-patient pan-cancer cohort; specific effect sizes for FGFR1 were not reported in the main text PMID:39506116.
  • Identified as somatically mutated in breast cancer WES cohort (Sanger Institute, 100 tumors); FGFR1 mutations and amplifications highlight receptor tyrosine kinase pathway dysregulation in breast cancer PMID:22722201
  • Focal amplification in lung squamous cell carcinoma (TCGA, 178 tumors); identified as a candidate therapeutic target PMID:22960745
  • Focal amplification in 6% of SCLC (29 tumors, CLCGP WES/WGS); potential therapeutic target PMID:22941188
  • Amplified in luminal B and HER2-enriched breast cancer subtypes (TCGA, 510 tumors) PMID:23000897
  • Amplified in the copy-number-high (serous-like) cluster 4 of endometrial cancer PMID:23636398
  • Recurrent kinase-domain hotspot mutations at N546 and K656 (5/96 WGS + 9/45 screening cohort) in pilocytic astrocytoma; plus a ~4.5 kb kinase-domain internal tandem duplication; mutants drive ERK phosphorylation; all FGFR1-mutant tumors extra-cerebellar/midline; same mutations recurred in 3/48 pediatric glioblastomas PMID:23817572
  • Recurrent amplification detected in high-grade urothelial bladder carcinoma (BLCA) as part of the MAPK-pathway alteration set (35% combined); arose in a predominantly mutually exclusive distribution with other RTK/RAS/RAF alterations PMID:23897969
  • FGFR1 alteration contributes to the RTK-alteration rate of 67.3% in GBM (TCGA 2013 cohort, n=251 with WES+CNA); FGFR2/3 combined were explicitly listed at 3.2%, and FGFR1 was identified as part of the RTK pathway alteration landscape PMID:24120142
  • Focal amplification in 11/53 ESCC validated by FISH; protein over-expression in 17.3% of tumors; proposed druggable target in ESCC PMID:24686850
  • Alterations observed in the low-grade dysplasia stage of PSC-associated CCA progression, suggesting an early role in biliary tract tumorigenesis. PMID:25526346
  • Focal amplification in 10% of HPV(-) vs 0% HPV(+) HNSCC PMID:25631445
  • Recurrent focal amplification in SCLC (110-tumour WGS cohort) PMID:26168399
  • Co-amplified with WHSC1L1 at 8p11.23 in 8% of primary prostate cancers PMID:26544944
  • MAPK-pathway alteration (with FGFR2, BRAF, NF1, NTRK1/2) enriched in PA-like LGG (52%) and LGm6-GBM (32%) in a pan-glioma TCGA methylation/genomic study (n=1122); FGFR1 alterations associated with pilocytic-astrocytoma-like IDH-wildtype LGG subtype with favorable prognosis PMID:26824661
  • Amplification at FGFR1/WHSC1L1 locus is among the candidate Ras/Raf/RTK pathway events that raise the fraction of lung ADCs with an actionable driver to 76%; enriched in oncogene-negative lung ADC PMID:27158780
  • FGFR1 N577K paired with H3F3A K27M in a pediatric glioma patient in the PIPseq cohort; FGFR1 alterations listed among targetable somatic events in high-risk pediatric cancers PMID:28007021.
  • Recurrent focal amplification in ESCC (alongside TERT, MDM2, NKX2-1) in the TCGA esophageal carcinoma multi-platform characterization PMID:28052061.
  • Somatic mutation identified in pheochromocytoma/paraganglioma (PCC/PGL) by cancer-relevant gene scan in the TCGA PCPG multi-platform study; grouped in the kinase signaling pathway axis alongside NF1, HRAS, RET, BRAF, and NGFR PMID:28162975.
  • Among potentially targetable kinases in CIN-subtype esophagogastric cancer; often concurrent with other actionable kinases suggesting combination strategies are needed PMID:29122777

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity data reported in the corpus for FGFR1 in osteosarcoma.

Therapeutic relevance

  • FGFR1 amplification in RT-OS may represent a targetable alteration, though no FGFR-directed therapy data are reported in this context PMID:37350195.
  • The FGFR1 downstream signature (NRP2, LRP4, TGFBI) could stratify bone-metastatic CRPC patients for FGFR-targeted therapy (e.g., dovitinib) PMID:38488813.
  • FGFR1 gain in SARC0133 RMS correlated with selective sensitivity to infigratinib but not dovitinib in PDTO screening, illustrating that FGFR inhibitor class is not interchangeable PMID:39305899.

Open questions

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22722201

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:22941188

This page was processed by crosslinker on 2026-05-14. - PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:23636398

This page was processed by crosslinker on 2026-05-14. - PMID:23817572

This page was processed by crosslinker on 2026-05-14. - PMID:23897969

This page was processed by crosslinker on 2026-05-14. - PMID:24120142

This page was processed by crosslinker on 2026-05-14. - PMID:24686850

This page was processed by crosslinker on 2026-05-14. - PMID:25526346

This page was processed by crosslinker on 2026-05-14. - PMID:25631445

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:26824661

This page was processed by wiki-cli on 2026-05-14. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14. - PMID:28052061

This page was processed by wiki-cli on 2026-05-14. - PMID:28162975

This page was processed by wiki-cli on 2026-05-14. - PMID:29122777

This page was processed by wiki-cli on 2026-05-15.