Figure 3

Loss of DNA methylation on the X chromosome. (A) Distribution of hypermethylated (gray) and hypomethylated DMRs (blue) on all chromosomes in EAC (left) and UPSC (right). (B) Global DNA methylation changes on the X chromosome. MeDIP-seq and MRE-seq RPKM values of seven samples were calculated at 500 kb resolution across the X chromosome. The averaged RPKM fold changes (cancer/normal) of each type (3 EACs and 3 UPSCs) were log2-transformed and plotted along with the X chromosome coordinate. (C) XIST expression in normal controls and pre-classified (grade: G1, G2, G3; microsatellite state, and subtype) endometrial cancer samples. Y-axis: calculated RPKM value based on mRNA-seq from TCGA. Asterisk indicates P <0.01, Student’s t-test. (D) DNA methylation distribution of 9,620 CpG sites on the X chromosome in pre-classified grade 3 (microsatellite state, and subtype) uterine corpus endometrial cancer samples (light blue: MSI-H type EAC patients; dark blue: MSS type EAC patients; red: MSS type UPSC patients. Infinium 450K platform) and normal controls (green, Infinium 450K platform). For each CpG site, the averaged DNA methylation level was calculated within the pre-classified group, and each boxplot represents distribution of the averaged methylation level of all 9,620 CpGs of the cancer groups and the normal controls. CpG sites with no value in any sample were removed. MSI-H: Microsatellite instability-high. MSS: Microsatellite stability. The Mann–Whitney U test was performed respectively for each cancer group when compared to normal controls.