Fig. 6: Gene expression and DNA methylation signatures of progressive or recurrent pediatric brain tumors associate with worse patient outcomes.

a Significant differences between initial tumor and recurrent or progressive tumors for total number of somatic SVs detected (left) and for average CGI probe methylation (right), based on paired analyses. P-values by paired t-test on log2-transformed and logit-transformed data, respectfully. Boxplots represent 5%, 25%, 50%, 75%, and 95%. b Overlap between CGI probes with methylation (meth.) higher in progressive or recurrent tumors and CGI probes (FDR < 10% paired t-test on logit-transformed data, with beta difference>0.1 for ten or more tumors) for which the corresponding gene had higher or lower expression (p < 0.01, paired t-test on log2-transformed data) in progressive or recurrent tumors. Enrichment p-values by chi-squared test. c Top, heat map of 890 genes differentially expressed (FDR < 10%, paired t-test on log2-transformed data) in recurrent or progressive tumors compared to the initial tumor, involving 124 recurrent or progressive tumors from 101 unique patients. Bottom, heat map of 5716 CGI probes differentially methylated (FDR < 10% paired t-test on logit-transformed data, with beta difference>0.1 for ten or more tumors). Expression or methylation values for each recurrent or progressive tumor represented are centered on the corresponding initial tumor. A subset of genes with both higher methylation and lower expression are listed off to the right. d Left, the gene expression signature from part c was applied to the expression profiles from the remaining CBTN pediatric brain tumor patients not used to define the signature (n = 1139 patients), associating with worse overall survival in these patients. Right, the DNA methylation signature from part c was applied to the methylation profiles from the remaining CBTN pediatric brain tumor patients not used to define the signature (n = 1049 patients), associating with worse survival. e The DNA methylation signature from part c was applied to the methylation profiles from TCGA adult pan-cancer patients (n = 8833 patients), associating with worse survival. For parts d and e, survival association p-values correct for histologic or cancer types.