Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Relative Spatial Homogeneity of Embryonal Brain Tumors of Childhood

Quiescent Sox2+ cells drive hierarchical growth and relapse in Sonic hedgehog subgroup medulloblastoma

Divergent clonal selection dominates medulloblastoma at recurrence

Medulloblastoma-associated DDX3 variant selectively alters the translational response to stress

CBP has opposing functions during cerebellar development and is a targetable tumor suppressor at late stages of medulloblastoma initiation

HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-driven Medulloblastoma

A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Highly recurrent U1 snRNA mutations drive alternative splicing in HH medulloblastoma

To further understand the biology of Sonic hedgehog medulloblastoma and its molecular subtypes, we studied 250 human Shh-MB using strand-specific RNA sequencing. We identified novel alterations within the cAMP dependent pathway and found that 18% of tumors have genetic events that directly target the abundance and/or stability of MYCN. We also discovered an extensive network of fusions in focally amplified regions, and several loss-of-function fusions in tumor suppressor genes PTCH, SUFU and NCOR1. Molecular convergence on a core of specific genes by nucleotide variants, copy number aberrations, and gene fusions highlights key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma.

We used single-cell transcriptomics to study cells from the developing human cerebellum, and show that different molecular subgroups of medulloblastoma resemble distinct glutamatergic progenitors.