The Transcriptional Regulatory Network of Proneural Glioma Determines the Genetic Alterations Selected during Tumor Progression

摘要: Proneural Glioblastoma is defined by an expression pattern resembling that of oligodendrocyte progenitor cells, and carries a distinctive set genetic alterations. Whether there functional relationship between the proneural phenotype associated alterations unknown. To evaluate this possible relationship, we performed longitudinal molecular characterization tumor progression in mouse model glioma. In setting, tumors acquired remarkably consistent deletions at late stages progression, similar to those deleted human Glioblastoma. Further investigations revealed p53 master regulator transcriptional network underlying phenotype. This p53-centric its were observed both early preceded proneural-specific deletions. Remarkably, deletion time initiation obviated acquisition later deletions, establishing link subtype-specific selected during glioma progression.