FGFR2

Overview

FGFR2 is a receptor tyrosine kinase whose activating fusions and mutations are actionable with FGFR inhibitors in multiple tumor types, but in urothelial carcinoma it is vanishingly rare compared with FGFR3.

Alterations observed in the corpus

  • Only 1/1,507 urothelial tumors had a potentially actionable FGFR2 alteration (an FGFR2:MARVELD3 fusion of unclear significance) in the MSK bladder_msk_2023 cohort PMID:37682528.
  • FGFR2 is an actionable driver in intrahepatic cholangiocarcinoma; the MSK hidden-genome classifier predicted overall survival in IHC independently of FGFR2 alteration status PMID:38864854.
  • In the MSK pdac_msk_2024 PDAC cohort (n = 2,336), FGFR2 was included among OncoKB-annotated actionable alterations tracked across MAPK-wild-type and other-MAPK-mutant subtypes; activating fusions involving MAPK-pathway genes (which include FGFR2) were nearly exclusive to KRAS-WT tumors (3.2% vs 0.04%, P = 2 × 10⁻³⁵) PMID:39753968.
  • FGFR2 mutations (I654V, D725V) detected at resistance to KRASG12C + EGFR inhibition in CRC patient ctDNA PMID:36355783
  • Mutated and focally amplified in breast cancer (TCGA, 510 tumors); alterations enriched in luminal subtypes PMID:23000897
  • Included in WNT/RTK MEMo module of mutual exclusivity with FBXW7 and ERBB2 in endometrial cancer subtype analysis PMID:23636398
  • Tandem duplication identified in one adenoid cystic carcinoma (ACC) tumor, similar to hematologic malignancy ITDs; no fusion transcript detected by RT-PCR PMID:23685749
  • Activating mutations p.Y376C, p.I389_V393>M (transmembrane in-frame deletion), and p.K642R (kinase domain) identified in adenoid cystic carcinoma; all paralogous to known activating germline craniosynostosis alleles or recurrent somatic activating alleles in endometrial/ovarian cancer; nominates FGFR inhibitors (e.g., dovitinib) as a therapeutic strategy PMID:23778141
  • K659E mutation (homologous to FGFR1 K656E) observed in a case reclassified from medulloblastoma to glioblastoma by expression profiling; co-occurring with FGFR3, TACC1/TACC3 fusions noted as background context for kinase-domain hotspot biology PMID:23817572
  • FGFR2/3 combined alteration frequency 3.2% in GBM (TCGA 2013 cohort, n=251 with WES+CNA), contributing to the RTK-alteration rate of 67.3% in that tumor type PMID:24120142
  • Mutated in 4/32 (13%) intrahepatic cholangiocarcinoma discovery-screen tumors at residues mutated in endometrial carcinoma; flagged as a potential therapeutic target via FGFR inhibitors then in clinical trials PMID:24185509
  • Altered in 9% of gastric adenocarcinoma (STAD) cases (TCGA); alteration type is RTK amplification enriched in the CIN subtype PMID:25079317
  • Fusions/rearrangements (BICC1, TACC3 partners) in 8–16% iCCA, 0–2% eCCA; targetable with pemigatinib (FIGHT-202 ORR 35.5%), infigratinib (ORR 37.9%), futibatinib (FOENIX-CCA2 ORR 42.0%); secondary kinase-domain mutations (N550, V565) emerge in ~60% on reversible inhibitors. PMID:25526346
  • Non-recurrent fusions detected in 2/484 papillary thyroid carcinoma (PTC) cases in TCGA cohort; mutually exclusive with BRAF/RAS/EIF1AX mutations. PMID:25417114
  • Recurrent fusions/rearrangements in intrahepatic CCA; futibatinib cited as an FGFR2 inhibitor synergizing with cisplatin in CCA PMID:25608663
  • Candidate RTK alteration in HNSCC across HPV groups (Fig. 3) PMID:25631445
  • Non-passenger mutation in breast adenoid cystic carcinoma (AdCC); shared with salivary gland AdCCs; part of FGF-pathway enrichment PMID:26095796
  • MAPK-pathway alteration (with FGFR1, BRAF, NF1, NTRK1/2) enriched in PA-like LGG (52%) and LGm6-GBM (32%) in a pan-glioma TCGA methylation/genomic study (n=1122); alterations associated with pilocytic-astrocytoma-like IDH-wildtype LGG subtype PMID:26824661
  • In-frame fusions (FGFR2-STK26, -TBC1D1, -WAC, -BICC1), a novel class of recurrent truncating rearrangements removing the 3’ UTR, indels (n=3), SNVs (n=10), and copy-gain (n=1) in cholangiocarcinoma; rearrangements exclusive to IDH/BAP1-bearing Cluster 4 (p < 0.001); aggregated alterations enriched in Cluster 4 (p < 0.01); FGFR2 3’ UTR deletions are a new mechanism of FGFR2 overexpression PMID:28667006
  • Oncogenic alterations in 5% of CIN-subtype esophagogastric cancers; listed among potentially targetable kinases PMID:29122777
  • FGFR2-BICC1 is the most recurrent fusion in CHOL (5.6% of samples); FGFR2 is a top recurrent 5-prime kinase fusion partner across 33 TCGA cancer types (9,624 samples); druggable in 15 cancer types per DEPO annotation. PMID:29617662

Cancer types (linked)

  • BLCA / UTUC — actionable FGFR2 alterations are essentially absent PMID:37682528.
  • PAAD — FGFR2 fusions/alterations included in the OncoKB actionability landscape of pdac_msk_2024; activating MAPK-gene fusions are enriched in KRAS-WT PDAC PMID:39753968.

Co-occurrence and mutual exclusivity

  • Not reported in the corpus.

Therapeutic relevance

  • In principle eligible for erdafitinib alongside FGFR3, but the near-absence of FGFR2 events in UC limits clinical impact in this disease PMID:37682528.

Open questions

  • Clinical significance of the observed FGFR2:MARVELD3 fusion is unclear PMID:37682528.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36355783

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:23685749

This page was processed by crosslinker on 2026-05-14. - PMID:23778141

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

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

This page was processed by crosslinker on 2026-05-14. - PMID:24185509

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

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

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14. - PMID:25608663

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

This page was processed by crosslinker on 2026-05-14. - PMID:26095796

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

This page was processed by wiki-cli on 2026-05-14. - PMID:28667006

This page was processed by wiki-cli on 2026-05-15. - PMID:29122777

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

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