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. Author manuscript; available in PMC: 2020 May 18.
Published in final edited form as: Nat Genet. 2019 Nov 18;51(12):1732–1740. doi: 10.1038/s41588-019-0525-5

Extended Data Fig.4. Mutational signatures associated to radiation and temozolomide.

Extended Data Fig.4

(a) HR-deficiency plays a key role in the appearance of an ID signature (SignatureAnalyzer-extracted) previously associated to radiation. Tumors in the top quartile of activity of HR signature (BRCAness signature) are considered HR-deficient, while tumors in the bottom quartile are deemed HR-proficient. The distribution of the number of IDs of this signature across HR-deficient and HR-proficient tumors either exposed or not exposed to radiation have been compared using a one-tailed Mann-Whitney test.

(b) MMR or MGMT-deficiency plays a key role in the generation of a TMZ-associated SBS signature. Left panel represents the load of TMZ-associated SBS in tumors exposed or unexposed to TMZ separated by their MMR status (considered defective with at least one protein-affecting mutation in an MMR-related gene). Right panel represents the load of TMZ-related exonic SBS in recurrent glioblastomas in an independent cohort exposed or not exposed to TMZ. TMZ-treated, non-MMR-deficient tumours have been split into two groups based on the methylation status of the MGMT promoter.