Figure 5

Differentially methylated regions and differentially expressed genes in CIMP+ relative to CIMP- samples from TCGA. (A) Proportion of gene-associated regions, CIMP + ^Hyper regions and CIMP + _Hypo regions overlapping CGIs, TSSs, 5′ UTRs, first exons, gene bodies, and 3′ UTRs. (B) Differentially expressed genes exhibiting significant correlation with methylation at associated CIMP + ^Hyper or CIMP + _Hypo regions. The 93 genes selected in the bottom panel overlapped at least one CIMP + ^Hyper or one CIMP + _Hypo region and exhibited significant levels of Spearman correlation (FDR < 0.10) in all the 12 cancer types that we analyzed. Top color bars shows genomic locations of probes within each of the 120 CIMP + ^Hyper and 1 CIMP + _Hypo regions overlapping one of those 93 genes. Top heat map shows differences in mean methylation for these 121 regions. Middle heat map shows values of Spearman correlation between methylation within these 121 regions and expression of the 93 associated genes. Bottom panel shows differential expression (Z-scores) for these 93 genes in CIMP+ vs. CIMP− samples, with red corresponding to genes with higher expression levels in CIMP+. Rows and columns in the bottom heat map were ordered according to average Z-score, decreasing from left to right and from top to bottom. Columns in the middle and top heat map were drawn so that genes associated to differentially methylated regions were shown in the same order as in the bottom heat map. Row order was also chosen to be the same as in the bottom heat map. The number of array probes located within each CIMP + ^Hyper or CIMP + _Hypo region is shown in parentheses after the corresponding gene name below the differential methylation heat map.