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. 2022 Jun 20;2(3):100188. doi: 10.1016/j.xops.2022.100188

Figure 4.

Figure 4

Methylation-driven differentially expressed genes in MYCN-amplified RB1-proficient retinoblastomas. MYCN-driven, RB1-proficient tumors display unique methylation-derived gene expression signatures that globally discriminate them from other retinoblastoma tumors. A, Heatmap showing hierarchal clustering for 40 genes that are hypermethylated (log2 fold change [FC] > 0; adjusted P < 0.05), downregulated (log2 FC < 0; adjusted P < 0.05), and indicate significant methylation-expression correlation (R < 0; q < 0.05) in MYCNARB1PRO retinoblastomas. The distinct expression of the 40 genes in MYCNARB1PRO samples primarily identified within a subset of the cohort (n = 15) is also reproducible in the entirety of the local retinoblastoma cohort (n = 47). For the expression of these genes, MYCNARB1PRO retinoblastomas (n = 4) show clear-cut separation from the rest of the retinoblastoma cohort (n = 47). B, Box-dot plots demonstrating normalized expression values of the top 4 hypermethylation-driven downregulated genes in MYCNARB1PRO versus the rest of the retinoblastoma cohort. C, Bar charts showing averaged expression of the 40 hypermethylated-driven genes discriminating MYCNARB1PRO retinoblastomas from other retinoblastoma subtypes: the current study (left) and public domain expression data (Liu et al10) including 62 retinoblastoma tumors (right). Red indicates MYCN-amplified RB1-proficient retinoblastomas. Green indicates MYCN-amplified RB1-deficient retinoblastomas. Blue indicates MYCN-silent retinoblastomas. Expression values are as normalized log2 robust multiarray average. D, Scatterplot depicting the association between MYCN expression and the mean expression of the 40 MYCNARB1PRO hypermethylation-driven downregulated genes in neuroblastoma (Pearson method). MYCN-amplified samples appear in red and MYCN-silent samples appear in blue. The dot sizes are adjusted by the expression level of MYCN. MYCN expression shows a significant negative correlation with the expression of the 40 signature genes (R = –0.604; P = 4.5 × 10–10). E, Box-dot plots for the normalized expression values of TSTD1 and CDKN2A within MYCN-amplified and silent neuroblastomas. Rb = retinoblastoma.