Figure 4. DNA methylation and histopathological tumor characteristics.

(a) Fraction of proliferating (MIB-1 positive) cells across transcriptional subtypes (Cla: classical, Mes: mesenchymal, Pro: proneural).

(b) Kaplan-Meier plots showing progression-free and overall survival stratified by the fraction of proliferating (MIB-1 positive) cells.

(c) ROC curves for DNA methylation based prediction of the fraction of proliferating (MIB-1 positive) cells. N denotes the number of tumor samples in each group.

(d) Clustered heatmap for the column-scaled DNA methylation levels of the most predictive genomic regions (5-kilobase tiling regions) from the classifier predicting the fraction of proliferating (MIB-1 positive) cells.

(e) Histogram showing the distribution of DNA methylation levels across the most predictive genomic regions from the classifier predicting the fraction of proliferating (MIB positive) cells.

(f) Average nuclear eccentricity (AVG) and its coefficient of variation (COV) for tumors that shift to a sarcoma-like phenotype during disease progression and those that retain a stable histological phenotype.

(g) Illustrative H&E stains of matched primary and recurring tumors from one patient that shifted to a sarcoma-like phenotype.

(h) Comparison of additional tumor properties (as indicated by the y-axis labels) between tumors that shifted to a sarcoma-like phenotype during disease progression and those that retained a stable histological phenotype.

(i) ROC curves for DNA methylation based prediction of average nuclear eccentricity (AVG) and its coefficient of variation (COV). N denotes the number of tumor samples in each group.

(j) Kaplan-Meier plots showing progression-free and overall survival stratified by whether or not their tumors shifted to a sarcoma-like phenotype.

The number of tumor samples (N) for the association tests (panels a, f, h) is provided in Supplementary Table 4.

The number of patients (N) in the Kaplan-Meier analysis (panels b, j) is provided in Supplementary Table 3.