Figure 6.
Cross-cancer analysis comparing TCGA cholangiocarcinoma, hepatocellular carcinoma, and pancreatic adenocarcinoma. A) Tumor Map analysis incorporating mRNA, methylation, and copy number showing proximity of each sample. B) COCA across miRNA, copy number, DNA methylation, RPPA, and Tumor Map for the 3 cancer types. Unsupervised clustering was performed within each datatype across a cohort of 292 samples from CCA, HCC, and PDAC to derive cross-tumor subtypes (miRNA n=4; Copy number (CN) n=5; DNA methylation (DNAmeth) n=7; RPPA n=6; Tumor Map n=7; see Fig. S6 for individual platform cluster solutions). Individual classification subtypes were then used as input for pan-tumor COCA analysis identifying 3 COCA classes (1st bar; K1, light green; K2, dark blue; K3, light blue). 2nd annotation bar denotes histology type – CCA, HCCC, PDAC. 3rd bar indicates the CCA-specific subtype classification (ECC, METH2, Meth3, and IDH, c.f. Figure 5). 4th bar notes IDH1 mutation status (red, R172 mutations; blue, R132 mutations; black, other mutations). 5th bar indicates samples with FGFR2 fusions. 6th bar indicates CCA score, a median value of the 600 most-enriched genes in CCA (see panel C). The bottom heatmap indicates sample membership for each of the individual classification subtypes (black, subtype member; white, not a subtype member; gray, missing data). Each row is labeled by platform and subtype number. (C) Six hundred genes enriched in cholangiocarcinoma-like hepatocellular carcinomas.