FGF19

Overview

FGF19 encodes fibroblast growth factor 19, a member of the endocrine FGF subfamily that signals through FGFR4. FGF19 is located at chromosome 11q13, a frequently amplified region in cancer, and its amplification often co-occurs with CCND1, FGF3, and FGF4 at the same amplicon.

Alterations observed in the corpus

  • FGF19 appeared in MSK-CHORD volcano plots of metastasis and Gleason-association analyses across the 24,950-patient pan-cancer real-world cohort (msk_chord_2024), indicating an association with metastatic tropism or disease aggressiveness; specific effect sizes and p-values for FGF19 individually were not reported in the main text PMID:39506116.
  • 11q13 focal amplification in HCC; provides therapeutic rationale for FGFR-targeted trials in a subset of HCC patients PMID:24735922
  • FGF19 undergoes high-level focal amplification in 5–10% of HCCs; oncogenic driver implicated in sorafenib resistance and a predictive biomarker (by IHC) for FGFR4 inhibitors BLU-554, H3B-6527, and FGF401; BLU-554 produced 16% ORR in FGFR4-driven (≥1% FGF19 IHC) patients vs 0% in FGFR4-negative. PMID:24798001
  • Intestinal FXR target (FGF15 in mouse) induced by Lactobacillus rhamnosus GG (LGG) to suppress bile acid synthesis; implicated in bile acid homeostasis in the cholangiocarcinoma microenvironment PMID:25608663
  • Co-amplified at 11q13.3 locus with FGF3, FGF4, and CCND1 in ~6% of HCC; focal amplification appears at advanced stages and is independently associated with poor survival PMID:25822088

Cancer types (linked)

  • NSCLC / LUAD — FGF19 flagged in metastasis-association volcano plots in the MSK-CHORD pan-cancer analysis PMID:39506116.

Co-occurrence and mutual exclusivity

  • FGF19 co-amplification with CCND1, FGF3, FGF4 at the 11q13 locus is a known biological phenomenon, but co-occurrence patterns were not specifically reported in the MSK-CHORD dataset for FGF19 PMID:39506116.

Therapeutic relevance

  • FGFR inhibitors (e.g., erdafitinib) are in clinical use for FGFR-altered cancers; FGF19 amplification may indicate sensitivity to FGFR4-directed strategies, but this was not tested in the citing paper.

Open questions

  • The specific metastasis-association signal for FGF19 in MSK-CHORD was not quantified in the main paper; supplementary volcano-plot data would be required to determine the direction and magnitude of the association PMID:39506116.

Sources

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