Figure 6.

Pediatric Cancers Exhibit Hypermethylation at ICRs but Not at Global CGIs

(A) Heatmap for DNA methylation levels at imprinted DMRs in human normal kidney samples, renal cell carcinomas (RCC), and Wilms' tumors. Color scale is shown for DNA methylation levels. Infinium 450K data of normal kidney tissues and Wilms' tumors were obtained from GEO: GSE59157. Those of RCCs were obtained from GEO: GSE70303.

(B) Box plots of DNA methylation levels at representative hypermethylated imprinted DMRs in Wilms' tumors. Solid lines in each box indicate the median. The bottom and top of the boxes are lower and upper quartiles, respectively. Whiskers extend to ±1.5 IQR. Note that H19 DMR and RB1 DMR are hypermethylated in Wilms' tumor but not in normal kidney or RCC. ^∗∗∗∗p < 0.0001 (Mann-Whitney U test).

(C) Box plot of DNA methylation levels at all CGIs in normal tissues, pediatric cancers, adult cancers, somatic cells, and PSCs. Solid lines in each box indicate the median. The bottom and top of the boxes are lower and upper quartiles, respectively. Whiskers extend to ±1.5 IQR. Note that increased CGI methylation is observed in adult cancers but not in pediatric cancers. Data of somatic cells and PSCs are the same as in Figure 4A.

(D) Hierarchical clustering analysis based on the methylation status at all CGIs.

(E) Box plot of DNA methylation levels at CGIs linked to PcG target genes (Lee et al., 2006) in normal tissues, pediatric cancers, adult cancers, somatic cells, and PSCs. Solid lines in each box indicate the median. The bottom and top of the boxes are lower and upper quartiles, respectively. Whiskers extend to ±1.5 IQR.