SMARCA5 is required for the development of granule cell neuron precursors and Sonic Hedgehog Medulloblastoma growth.

ABSTRACT: Medulloblastoma constitutes a molecularly diverse group of malignant embryonal brain tumors. Sonic hedgehog molecular group of medulloblastoma (SHH-MB) is a highly heterogeneous tumor entity, characterized by constitutive activation of the SHH signaling pathway. Due to lack of suitable cell line models, little is known about genetic dependencies in SHH-MB outside of the SHH pathway. By performing a CRISPR-Cas9 dropout screen in SMB21 cells derived from SHH-MB in Ptch^+/- mice, we aimed to identify genetic vulnerabilities in SHH-MB. Among the top scored gene hits, members of the SNF2-family of ATP-dependent chromatin remodelers including Smarca5 emerged as genetic dependencies in SHH-MB, and we validate that Smarca5 knockout inhibits SHH pathway activation and SHH-MB cell prolifer

SUBMITTER: Tsiami F 

PROVIDER: S-EPMC12274346 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature