Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

摘要: Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely key to understanding treatment failure. However, extent as result tumor evolution still poorly understood. To address this, we developed unique surgical multisampling scheme collect spatially distinct fragments from 11 GB patients. We present an integrated genomic analysis uncovers extensive heterogeneity, patients displaying different subtypes within same tumor. Moreover, reconstructed phylogeny for each patient, identifying copy number alterations in EGFR CDKN2A/B/p14ARF early events, aberrations PDGFRA PTEN later events during cancer progression. also characterized clonal organization fragment at single-molecule level, detecting multiple coexisting cell lineages. Our results reveal genome-wide architecture variability across spatial scales patient-specific patterns evolution, consequences design.