Fig. 8: Evolution of PCPG under treatment pressure.

A Clinical timeline of for patient E169. Bi Shared and private coding, non-coding/synonymous (NC/Syn.), and structural (SV) variants between paired metastases taken before and after CVD treatment. Bii Copy number status along each chromosome (y-axis) in paired metastases (x-axis). C Mutation signature analysis using COSMIC v3 SBS (i) and InDel (ii) signatures (y-axis) in paired metastases (x-axis). Heatmap colour indicates signature contribution. D Expression of MGMT in the A5 cohort. E–G Patient E167, see description for panels (B, C). H Expression of MLH1 in the A5 cohort. I Total mutation counts (y-axis) for PCPG tumours (x-axis) in the Project GENIE data registry. Bar colour indicates the presence of a mutation in the mismatch repair pathway. J Trinucleotide context for mutations observed in E167-M1 (top), E167-M2 (second from top), the highest mutation load tumour from the GENIE dataset (second from bottom), and ctDNA derived from a patient with metastatic SHDB-related PGL treated with Temozolomide. K¹⁸F-FDG-PET imaging for Temozolomide treated patient at time of blood draw for cfDNA analysis. L IchorCNA analysis of ctDNA derived from Temozolomide treated patient (M) Variant allele frequencies (y-axis) for somatic variants (x-axis) observed in ctDNA derived from Temozolomide treated patient. Datapoints are coloured to indicate transition/transversion or insertion/deletion type.