Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.

ABSTRACT: Paediatric medulloblastomas with chromothripsis are characterised by high genomic instability and are among the tumours with the worst prognosis. However, the molecular makeup and the determinants of the aggressiveness of chromothriptic medulloblastoma are not well understood. Here, we apply spatial transcriptomics to profile a cohort of 13 chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup. Our data reveal a higher extent of spatial intra-tumour heterogeneity in chromothriptic medulloblastomas compared to non-chromothripictic tumours, which is associated with increased proliferation and stemness, but lower immune infiltration and differentiation. Spatial mapping of genetic subclones of the same tumour identify a regionally distinct architecture and clo

SUBMITTER: Kats I 

PROVIDER: S-EPMC11604656 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature