Fig. 4

DNA repair is affected upon IDHmut astrocytoma progression. a The proportions of different microhomologous sequence lengths in SV breakpoint junctions. Clonal SVs are visualized on the left, and all SVs are on the right. b Heatmap of gene set activities in the TCGA IDHmut astrocytomas show distinct activity patterns for MMEJ and NHEJ when compared to proliferation (S- and G2/M-phase). Samples are ordered based on the G2/M gene set activity in each tumor group. c DNA repair gene set activities increase with increasing grade in TCGA IDHmut astrocytomas, especially in grade 4. **p < 0.01, ***p < 0.001, and ****p < 0.0001, Wilcoxon rank-sum test. d DNA repair and proliferation gene set activities were increased upon progression, especially in TG04–TG06, in our discovery cohort. The DNA copy number status of CDKN2A and RB1 is marked on the right side of the heatmap. e Oncoprint showing alterations in DNA repair-related genes with progression-related alterations associated with gene expression in our and the TCGA data. f RAD51B expression was higher in TG05a, which was collected after radiation, compared to the grade 4 tumors that were also taken post-radiation. RAD51B expression was decreased and gene hemizygously deleted in grade 4 TG05b tumor. g Hemizygous loss of RAD51B was associated with worse OS in the TCGA IDHmut astrocytomas (p = 0.019, log-rank test). h Heterogeneous treatment paths in grade 2 cohort. The survival cohort comprises 43 patients diagnosed with a grade 2 IDHmut astrocytoma, 29 of which were surgically reoperated and nine progressed to grade 4. Residual tumor information after primary operation (*) was available from 23 patients. i Patients with primary grade 3 IDHmut astrocytoma were mainly treated with postoperative radiation or combination therapy. Timelines of 32 patients, 10 of which were treated surgically for relapse and eight progressed to grade 4. Residual tumor information after primary operation (*) was available from 13 patients