Fig. 10: Noncanonical somatic mutation associations with MYC family alterations.

a Schematic of approach to identify somatic mutations (SNVs or indels) associated with a given pathway. Taking the set of tumors with high pathway signature scoring but with no canonical mutations (based on Fig. 7), we consider noncanonical genes for enrichment of mutations. Results are compared between the proteomic compendium and The Cancer Genome Atlas (TCGA), where we observed significant overlap between the respective gene-level associations (p < 5E−8, one-sided Fisher’s exact test). b List of top mutated genes overlapping between proteomic compendium and TCGA results (p < 0.01 and p < 0.001, respectively, one-sided Fisher’s exact test). Results involve 12 genes with mutation events enriched within tumors with high MYC signature but no MYC or MYCN copy gain or amplification. c Across both the proteomic compendium (left) and TCGA (right) tumor datasets, heat maps of MYC/MYCN copy alteration and of somatic mutation (SNV or indel) in genes from b. SD standard deviation from the median. Cancer type color bar legend defined in d. d Box plots of MYC/MYCN signature scores by alteration class in proteomic compendium (left) and TCGA (right) tumor datasets. p values versus unaligned group (tumors with none of the listed alterations) by t-test. Box plots represent 5% (lower whisker), 25% (lower box), 50% (median), 75% (upper box), and 95% (upper whisker). n = biologically independent tumors. Cancer type represents TCGA project name.