Supplemental Figure 2 from TumorMap: Exploring the Molecular Similarities of Cancer Samples in an Interactive Portal
Molecular subtype visualization. Known biology recapitulated by the mRNA expression map. (A) BRCA molecular subtypes and their layout in the map. The map shows that tumors of the same molecular subtype tend to cluster together, with very little mixing of those subtypes, indicating that those subtypes are indeed molecularly different. (B) Estrogen signaling (yellow) and basal signaling (blue) are the top differentiating programs between the basal and non-basal BRCA tumors. Very few tumors exhibit signals of both programs (green). The group of samples labeled as Basal subtype in part A predominantly exhibits the basal signaling program and the group of samples consisting of LumA (for luminal A) and LumB (for luminal B) in part A predominantly exhibits the estrogen signaling program. (C) Association of TP53 mutations (blue) with basal breast tumors and PIK3CA mutations (yellow) with luminal tumors demonstrates at-a-glance view of genomic event association with molecular subtypes in the map. Samples that exhibit both mutations are shown in green. (D) COAD and READ tumors cluster together (left) and the map separates genomically stable and unstable tumors (right). (E) BLCA tumors separate into three previously discovered molecular subtypes. These subtypes are BLCA-core, BLCA-lung-like, and BLCA-squamous-like. (F) KIRC tumors are deficient in MSH2 (activity level indicated by the intensity of yellow), a component of the DNA mismatch repair pathway. This is a known characterization of KIRC tumors. (G) Co-occurrence of VHL mutations (green) and high HIF1A activity (indicated by the intensity of yellow) in KIRC tumors. Samples colored in yellow indicate an absence of VHL mutation but high HIF1A activity. Samples colored in green indicate both the presence of VHL mutation and high HIF1A activity. No samples show a presence of VHL mutation and low HIF1A activity (such samples would be colored in blue). (H) Spatial correlation analysis (SCA). Mutual exclusivity of RB1 mutations and CDKN2A deletions. These two events do not co-occur in the same patients even when they occur in patients clustering in the same regions of the map. (I) SCA - positive spatial correlation of RB1 mutations and PTEN mutations. In regions of the map where both of these events occur, they tend to occur in the same patients. (J) The overlap in gene signatures distinctive of the Tumor Map's relative positioning of BRCA molecular subtypes. HER2+ tumors share more differentially expressed genes in common between luminal than basal tumors. The subtype groupings are defined by BRCA sample annotations. Differential expression analysis resulted in 150-gene signatures for each subtype. Venn-diagram of these gene signatures shows the overlap between gene sets for each of the subtype.