Fig. 3

Progression-related CDKN2A/RB1 alterations were associated with postoperative combination therapy and PDGFRA/MET alterations. a DNA copy number patterns of patients TG01–TG05 in grade 2–3 (left column) and grade 4 (right column) tumors. b Number of copy number losses was increased upon progression to grade 4, especially in cases without a hypermutator phenotype. c Summary of tumor characteristics, patient treatment, and genetic alterations in cases TG01–TG06. Narrow columns represent samples not included in the discovery cohort. d CDKN2A and RB1 were homozygously deleted either through simple rearrangements (TG02b) or complex rearrangement patterns. Rearrangements that were already called in grade 2–3 tumors are visualized in gray. Uncalled rearrangements (dashed lines) were aligned to repeat segments (yellow triangles) in TG05b. e Short microhomologous sequences were detected in rearrangements involved in the reported DNA copy number alterations. f Alterations and treatment information in the targeted sequencing validation cohort consisting of IDHmut astrocytomas, including four discovery cohort cases. Only point mutations, amplifications, and full deletions were analyzed. Narrow columns represent samples with no targeted sequencing data. Relapses after progression to grade 4 are not shown. g Patients who underwent both radiation and chemotherapy after surgery were more likely to develop CDKN2A/RB1 inactivation compared to patients who received radiotherapy alone in the combined discovery and targeted sequencing cohort. Only cases with complete treatment information until progression and confirmed event of inactivation upon progression were included. Inactivating alterations in CDKN2A and RB1 are shown separately but were counted together for Fisher´s exact test. h Rearrangement patterns in PDGFRA and MET genes. The rearrangement at the start of PDGFRA amplification in TG02b is located in the centromere and not called because of satellite repeats (yellow triangles). In TG05, PDGFRA was amplified as an extrachromosomal DNA. PTPRZ1-MET fusion was detected from subclonal rearrangements in TG03b. Uncalled and subclonal rearrangements (dashed arrows and arcs) are only visualized when affecting the alteration