Extended Data Fig. 3. Mutational signatures associated with RT.
a-d. Distribution of indel types for post-treatment mutations in the GLASS cohort, separated by RT (a, c, RT- negative; b, d, RT-treated) and HM (a-b, Hypermutator; c-d, Non-Hypermutator). Note that patterns of indels in hypermutated samples resemble the previously identified MSI signature ID2, whereas RT-treated Non-Hypermutant gliomas harbor large similarities with ID8. Sample sizes for each subgroup are annotated.
e. Comprehensive comparison of all 17 COSMIC indel (ID) signatures in IDHmut glioma. Top 2 panels display longitudinal comparison of absolute signature contributions separated by radiation treatment (RT+ and RT−). Middle 2 panels display longitudinal comparison of relative signature contributions separated by radiation treatment. For these panels two-sided Mann-Whitney U test was applied for statistical testing. (ns = not significant, * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001). Note that ID8 is the only signature consistently associated with radiation therapy across different comparisons, nominating it as a robust signature of radiotherapy. Boxes span quartiles, center lines as medians, whiskers represent absolute range, excluding outliers.
f. Absolute (top) and relative (bottom) contribution of ID8 signature in metastatic cohort compared between cases with prior radiation treatment and cases without prior radiation treatment separated by tumor types. Note that most tumor types show significantly higher values of the signature in curative RT+ cases. Two-sided Kruskal-Wallis test was applied for statistical testing. Boxes span quartiles, center lines as medians, whiskers represent absolute range, excluding outliers.