Fig. 5: SSVs associated with key oncogenic or tumor-suppressive pathways.

a Genomic rearrangements (represented in circos plots) involving Receptor Tyrosine Kinase (RTK) pathway-related genes (KRAS, MET, EGFR, NF1), p53/Rb-related genes (CDK4), TERT, SWI/SNF (SMARCB1), MYC family genes (MYC, MYCN, MYB), and HIPPO pathway-related genes (NF2). SSV events are colored according to tumor type, as indicated. b Pathway-centric view of somatic alterations in pediatric brain tumors (representing 558 CBTTC tumors and 507 patients with at least one somatic alteration in the indicated pathways), involving key pathways and genes previously annotated across multiple cancer types based on domain knowledge^19,21,36,37. Panel on the right represents the significance of enrichment (one-sided Fisher’s exact test) of gene alteration events for each pathway within any particular tumor type versus the rest of the tumors (focusing on the 13 tumor types with the most tumors). c For the pathways from b that also involve at least one SSV event, somatic alteration events involving each gene included in the pathway are represented. For SSV-impacted genes the corresponding differential mRNA expression patterns are shown. For a, b, events are colored according to the type of somatic alteration: gene fusion, SSV (for oncogenes, breakpoint falling with 1 Mb of gene and associated with expression >0.4 SD from median for the given tumor; for tumor suppressors, breakpoint falling within the gene body and expression < −0.4 SD), SNV or indel (for oncogenes, SNV within hotspot residue⁴⁹; for tumor suppressor genes, SNV within hotspot residue or inactivating mutation by indel/nonsense/nonstop), and deep deletion or high-level amplification (respectively approximating total copy loss and copy levels more than 2× greater than that of wild-type, based on thresholded values).