Aberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma.

ABSTRACT: Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, Suppressor of Fused (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 SUFU 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 FGF5 expression is uniquely upregulated in infantile MB^SHH tumors. Similarly, mice lacking SUFU (Sufu-cKO) ectopically express Fgf5 specifically along the secondary fissure where GNPs harbor preneoplastic lesions and show that FGFR signaling is also ectopically activated in this region.

SUBMITTER: Yabut OR 

PROVIDER: S-EPMC11750132 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature