Four expression defect classes. (A) Integrative analysis of differential gene expression and methylation in eight IDHwt glioma samples identified four main defect classes: gain of expression with gain of methylation (Meth+/Exp+), gain of expression with CGI/promoter remaining unmethylated (No Meth/Exp+), loss of expression with gain of methylation (Meth+/Exp−), and loss of expression with the CGI/promoter remaining unmethylated (No Meth/Exp−). (B) Differential DNA methylation analysis in all IDHwt glioma samples (n = 55) versus controls (n = 8) (delta of the mean β-value). Glioma samples were grouped in the four classes of expression defects defined in A. The methylated and methylable status of genes is indicated in the left column. (C) Integrative analysis of differential expression and methylation at selected Meth+/Exp+ (upper), No Meth/Exp+ (middle), and No Meth/Exp− (lower) genes in 42 IDHwt glioma samples compared with controls (n = 8). (D) Integrative analysis of differential gene expression and methylation in an independent cohort of 135 IDHwt glioma samples (validation cohort) also identified the four main defect classes. Odds ratio and significance of the overlap (Fisher's exact test) between the data of the validation cohort and our cohort, for each defect category, are shown on the right panel.
