biostudies-literatureMathur RNIMH NIH HHSNHGRI NIH HHSNCI NIH HHSNINDS NIH HHSNIGMS NIH HHS446-463.e16https://www.ebi.ac.uk/biostudies/studies/S-EPMC10832360biostudies-literatureUnknown187(2)Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and coCellGlioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.PMC10832360P50 CA097257R01 MH113896U01 CA229345R01 HG009906T32 CA151022R50 CA274229R01 HG011207R01 CA169316R35 GM124820F32 CA239472R35 NS105068P01 CA118816R01 CA244621R01 MH123156Hou YWang JSolomon DAPhillips JJStasiak LAYue FWang QHervey-Jumper SLLafontaine MCostello JFChang SMOkada HJin QOldham MCLupo JMSmirnov IVGallo MYamaguchi TNBerger MSSchupp PGMathur RHong CKwok DStevers NOYoungblood MWNikolic AHilz SShai ABoutros PCGrishanina NRfalseGlioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and co2024-01-01T00:00:00Z2024 Jan2025-04-03T23:36:22.459Z2025-04-03T23:36:22.459ZS-EPMC108323603824208710.1016/j.cell.2023.12.013