Figure 1

(A) Somatic mutational and SCNA landscape of PAs. Tumor subtypes based on hormone secretion profile, patient age and gender, mutations in recurrently-mutated genes, number of mutations in each tumor subtype and relative number of different single-nucleotide substitutions in each tumor subtype are shown for 125 PAs. Copy number gain of SYCP1, SYCP2, and RAD21L1, as well as overall percentage of the genome disrupted by copy number variations, are all shown based on GISTIC analysis. (B) Significantly enriched pathways in each subtype based on pathway enrichment analysis. Bipartite network of the association between subtypes and pathways, where a yellow node represents a subtype, a pink node represents a pathway, and the line between these two types of nodes indicates that the pathway was significantly (P < 0.05) associated with the subtype. Blue lines illustrate associations between a PA subtype and a molecular pathway based on our data in combination with previous whole-exome sequence data. The green lines show the associations between PA subtypes and well-known pathways based on prior publications. (C) Interconnections between each subtype based on pathway analysis. Each pair of subtypes is linked by a line with width corresponding to the number of pathways (containing at least two mutated genes) shared by both subtypes. Node size reflects the number of pathways shared by any other subtypes. (D) The landscape of potential drug targets in 125 PAs. Genes encoding potential drug targets in seven altered pathways are shown. Genes mutated in PAs in this study are shown in ovals. Genes in blue ovals indicate cancer-related genes. Gene names in brown indicate potential drug targets, with their FDA-approved drugs shown in adjacent brown boxes. Orange stars indicate that drugs tested in phases I-III clinical trials are available to target the gene.