Extended Data Fig. 4: Effects of radiotherapy on structural variants.

a, Analysis of structural variants (SVs) in glioma samples (Translocations, Duplications, Deletions, Inversions). For each patient, number of SVs were calculated pre-and post-treatment and the proportional increase after therapy for each SV- type was plotted separately for RT-naive and RT-treated samples. Based on the distribution of proportional increase from primary to recurrence, a cutoff was defined for >50% increase that was further used for analyses in Fig. 4a. b, To support analyses presented in Fig. 4a, a multivariable logistic regression model was fitted for the >50% increase values of the structural variant types. Two-sided Wald test. This model includes radiation therapy, temozolomide therapy, molecular subtype and surgical interval as variables. c, Schematic overview of separation of aneuploidy events into whole chromosome aneuploidy as a result of simple segregation errors and partial aneuploidy as a result of complex segregation errors. d, Longitudinal analysis of partial aneuploidy in IDHmut glioma samples. Dots are proportional to the frequency of whole chromosome loss integer for each subgroup. Two-sided paired Wilcoxon rank-signed test. e, Multivariable Poisson regression model for whole chromosome losses in IDHmut glioma including molecular subtype, RT, TMZ, surgical interval and CDKN2A status at recurrence as variables. Two-sided Wald test. Note that CDKN2A homdel, but not RT is independently associated with higher whole chromosome losses. f, Density plots over integers of whole chromosome deletion scores for comparison between primary vs recurrent glioma samples, separated by radiotherapy. g, Density plots over integers of whole chromosome deletion scores for comparison between RT-naïve vs RT + pal vs RT + cur and/or CDKN2A homdel vs. wild-type (WT) samples from the HMF dataset. Note that CDKN2A homdel is associated with higher whole chromosome deletion scores, independent of RT. Within samples with CDKN2A homdel, samples that were RT-treated with curative intent show the highest deletion scores.