Figure 5.

Genomic characterization and subsequent xenografting and treatment of an ultrahypermutant childhood glioblastoma. A, Schematic of experiments performed on a CMMRD pediatric glioblastoma. B, Subclonal analysis reveals multiple mutations per clone. C, Identity of RAS/MAPK pathway–related alterations in this tumor. D, Mutational signature analysis reveals the source of mutations as RRD. E, Primary culturing of cells derived from this tumor, without prior culturing, and treatment with either trametinib or selumetinib. F, Survival experiment following flank implantation of this ultrahypermutant GBM and subsequent treatment in vivo with trametinib. G, A second set of flank engraftment experiments were conducted to assess tumor growth following flank implantation and treatment with trametinib or selumetinib. Arrow indicates time at which treatment commenced.