Mutational landscape and clonal architecture in grade II and III gliomas

摘要: Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors. Despite recent findings frequent mutations in IDH1 other genes, knowledge about their pathogenesis is still incomplete. Here, combining two large sets high-throughput sequencing data, we delineate the entire picture genetic alterations affected pathways these glioma types, with sensitive detection driver genes. comprise three distinct subtypes characterized by discrete clinical behaviors. Mutations showed significant positive negative correlations a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there functional interplay between drive clonal selection. Extensive serial multi-regional sampling analyses further supported this finding also identified high degree temporal spatial heterogeneity generated during tumor expansion relapse, likely shaped complex but ordered processes multiple selection evolutionary events.