PTEN restrains SHH medulloblastma growth through cell autonomous and nonautonomous mechanisms.

ABSTRACT: A third of patients with the pediatric cerebellar tumor Medulloblastoma (MB) have mutations that activate Sonic hedgehog (SHH) signaling (SHH-MB subgroup). The contribution of secondary mutations to tumor severity is not clear. PTEN mutations are enriched in the SHH-1 subtype that has the lowest survival rate. Heterozygous loss of Pten in two constitutive SHH-MB mouse models increases penetrance and excellerates onset of differentiated tumors. We used a sporadic mouse model of SHH-MB expressing oncogenic SmoM2 in cerebellar granule cell precursors (GCPs) and scRNA-seq to delineates cellular and transcriptional changes that accelerate tumor growth and cause differentiation. Homozygous but not heterozygous loss of Pten leads to rapid acceleration of tumor growth and end

SUBMITTER: Lao Z 

PROVIDER: S-EPMC12324473 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature