Fig. 7. Counteracting epigenetic imbalance in MYC tumors through targeted therapy.

A Eight human RT cell lines (3 for SHH and 5 for MYC subgroups) was tested for viability after 6 days decitabine (DAC) treatment (1 µM). A remarkable decrease in cell viability was observed in both subgroups, though the effect on MYC cells was more pronounced. (Unpaired-t-test, two-tailed, *p = 0.064). For each box, the lower and upper bounds represent the 25th and 75th percentiles; the center corresponds to the 50th percentile (median). The whiskers go down to the smallest value and up to the largest. B Graph depicts the cell number of DAC-treated BT16 (ATRT-MYC) cells over time. n = 2/3 technical replicates. Mean ± SD is shown; gray dots indicate individual values. C Overrepresented functional categories of up- and downregulated DEGs of DAC-treated BT16 cells over 14 days compared to untreated cells, further subjected to microarray profiling. Functional categories are clustered and visualized based on similarity using REVIGO⁹⁹. Size and color of circles represents the p values (log10 scale) derived from ToppGene⁸⁷ (statistical method as probability density function) considering terms enriched with an adjusted p-value (FDR) < 0.05. D GO term analysis of DEGs between BT16 cells before and after SMARCB1 re-expression (BT16 + DOX) (data derived from Wang et al.⁵⁹). Differential expression analysis was conducted with the R package DESeq2⁹⁵. Only genes with adjusted p-value < 0.05 were considered (Benjamini–Hochberg correction). Functional annotation was performed as in (C). Only significantly enriched GO terms were considered (x-axis, −log10 scale). E Stacked bar graph depicts cell cycle analysis of BT16 cells treated with vehicle or DAC over time. Analysis based on n = 2/3 technical replicates, mean ± SD is shown. F Stacked bar graphs showing apoptosis assay results of BT16 or G401 tumor cells treated with DAC or AZA (5-azacytidine) over 7 days. n = 3 technical replicates, mean ± SD is shown. Tumor volume curve of G NOD/SCID mice (engraftment of G401 cells) treated with DAC (n = 6) or vehicle (n = 8) (Unpaired, two-tailed T-Test; *p = 0.0258) and H of a PDX model of a relapsed eRT treated with vehicle (n = 7) or DAC (n = 7) (Unpaired multiple T-test; **p < 0.001, ***p < 0.001). See also source data file.