Fig. 1: MYCN-driven retinoblastomas have distinct molecular (epi)genetic and clinical features.

a Flowchart displaying method of DNA methylation data clustering. The flowchart summarizes the steps performed to build a threshold graph reflecting consensus clustering of the DNA methylation data from 61 retinoblastomas. b Separation of 3 retinoblastoma clusters by global DNA methylation-based consensus clustering (62 datasets of retinoblastomas), cluster A (n = 35, green), cluster B (n = 17, turquoise) and cluster C (n = 10, magenta). MYCN-driven cluster retinoblastoma included RB1^−/−MYCN^A (pink, n = 2), RB1-proficient MYCN^A (purple, n = 6), and RB1^−/−non-MYCN^A (maroon, n = 2). c How molecular tumor and clinical characteristics in the 61 patients with retinoblastoma differed in between the 3 clusters and correlation of clustering with the 2 subtypes grouped by the 8-CpG classifier¹² (Supplementary Data 1). d The numbers of differentially methylated CpG sites (Welsh t-test; abs.diff 0.2; Benjamini–Hochberg adjusted p < 0.001) in and outside of CpG islands (CpGi) are listed. e Differentially methylated CpGs in cluster C compared to cluster A|B and in cluster B compared to cluster A|C are depicted in the 2 heatmaps. f Density plots for DNA methylation levels (ß-values) of differentially methylated probes in cluster C vs. cluster A|B (left) and cluster B vs. cluster A|C (right). Inlet plots represent median density plots per cluster.