biostudies-literatureYabut ORNIH/NCINIMH NIH HHSAmerican Brain Tumor AssociationNCI NIH HHSNINDS NIH HHSNational Institutes of HealthNIH HHSRP100767https://www.ebi.ac.uk/biostudies/studies/S-EPMC11750132biostudies-literatureUnknown13Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, <i>Suppressor of Fused</i> (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MB^SHH). However, how different molecular lesions in the Shh pathway drive transformation is frequently unclear, and <i>SUFU</i> mutations in the cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) signaling is integral for many infantile MB^SHH cases and that <i>FGF5</i> expression is uniquely upregulated in infantile MB^SHH tumors. Similarly, mice lacking SUFU (Sufu-cKO) ectopically express <i>Fgf5</i> specifically along the secondary fissure where GNPs harbor preneoplastic lesions and show that FGFR signaling is also ectopically activated in this region.eLifeAberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma.PMC11750132R01 MH077694R01MH077694-S1K01CA201068A131363K01 CA201068R01MH077694R01 NS118995R01NS118995Ngo TPleasure SJGomez HGCastillo JGArela JYabut ORfalseAberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma.Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, <i>Suppressor of Fused</i> (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MB^SHH). However, how different molecular lesions in the Shh pathway drive transformation is frequently unclear, and <i>SUFU</i> mutations in the cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) signaling is integral for many infantile MB^SHH cases and that <i>FGF5</i> expression is uniquely upregulated in infantile MB^SHH tumors. Similarly, mice lacking SUFU (Sufu-cKO) ectopically express <i>Fgf5</i> specifically along the secondary fissure where GNPs harbor preneoplastic lesions and show that FGFR signaling is also ectopically activated in this region.2025-01-01T00:00:00Z2025 Jan2026-06-02T10:19:56.279Z2025-04-03T23:36:26.91ZS-EPMC117501323983577510.7554/eLife.100767