Fig 3.
Unsupervised hierarchical clustering (UHC) of diffuse intrinsic pontine glioma (DIPG) showed subgroups similar to those previously identified in adult and pediatric high-grade gliomas. (A) Dendrogram of UHC using top 1,000 most variable probe sets selected using median absolute deviation scores, and heat map featuring top 150 signature probe sets of each subgroup. Three main subgroups were identified. Tumors with focal gains of components in receptor tyrosine kinase (RTK)/phosphoinositide 3-kinase (PI3K) or retinoblastoma protein (RB) pathway are indicated in red at top of heat map. (B, C, D) Gene set enrichment analysis to evaluate coordinate expression in DIPG of gene sets defining subclasses of adult and pediatric high-grade gliomas6,22 showed that DIPG subgroups identified by UHC are highly similar to subgroups previously identified. Plots of running enrichment scores showed highly significant enrichment of mesenchymal markers22 in HC1, proliferative markers22 in HC2, and pediatric proneural markers6 in HC3; 33,928 genes were analyzed. (B) 132 genes in gene set; P = 0, false discovery rate (FDR) = .00162. (C) 176 genes in gene set; P = .0457, FDR = .216. (D) 616 genes in gene set; P = 0, FDR = .0445.