DNA methylation analyses in PCNSL as compared to hematopoietic controls and systemic DLBCL. (A) Principal Components Analysis (PCA) significantly separates control samples (blue circles) from PCNSL (orange circles) and systemic DLBCL (yellow circles) (p = 1.2 × 10-12; q = 3.9157 × 10-11) [40, 41]. (B) Heatmap generated by applying the same conditions as in (A) red: high methylation level, green: low methylation level; blue squares: hematopoietic controls, orange squares: PCNSL; Hematopoieteic controls have been analysed in replicates and are shown as individual samples demonstrating good reproducibility (C) Hierachical cluster analysis of DNA methylation data obtained from the 296 CpG loci (corresponding to 194 genes) differentially methylated between five PCNSL (orange) and 10 hematopoietic controls (blue) including 49 systemic DLBCL (yellow boxes). CpGs differentially methylated in PCNSL and normal controls did not distinguish between PCNSL and systemic DLBCL. (D) Unsupervised hierarchical cluster analysis of methylation values of all 1,284 CpGs from 10 hematopoietic controls (blue boxes), five PCNSL (orange boxes) and 49 systemic DLBCL (yellow boxes). While normal and malignant samples were delineated according to their DNA methylation pattern, PCNSL and systemic DLBCL did not segregate.