Fig. 1.

The frequency and prognostic significance of TMZ-associated hypermutation in IDH-mutant LGG. Panels A-D describe data from the cohort of gliomas sequenced at recurrence. (A) Among all sequenced tumors, highest histologically confirmed grade at re-resection for HM and non-HM tumors. (B) Proportion of transformed tumors exposed to TMZ that were hypermutated, stratified by subtype. (C) Time from diagnosis to transformation stratified by subtype, hypermutation status, and prior radiotherapy. (D) Timelines of prior TMZ exposure. Black lines represent a time from initial diagnosis to time of transformation (time zero). Red and blue bars represent TMZ exposure for HM vs non-HM tumors. Many patients received multiple courses of TMZ. Density plots of TMZ exposure are shown below the patient timelines. Abbreviations: Astro, IDH-mutant astrocytoma; HM, hypermutated; IDH, isocitrate dehydrogenase; LGG, low-grade glioma; Oligo, IDH-mutant 1p/19q co-deleted oligodendroglioma; N.S., non-significant; TMZ, temozolomide. * indicates significant result with P < .05.