Extended Data Fig. 2: Distributions of TMB, homopolymer indels, and SNV mutation spectra in the datasets used.
From: Mechanisms and therapeutic implications of hypermutation in gliomas
a, DFCI-Profile (de novo gliomas only); b, MSKCC-IMPACT; c, FMI (total n = 9,938). After examining the distribution of TMB in each dataset for breakpoints, thresholds for hypermutation were further confirmed using segmented linear regression analysis (analysis restricted to de novo gliomas for DFCI-Profile). This method showed the presence of a breakpoint at 17.0 and 8.7 mutations per Mb for the DFCI-Profile and FMI datasets, respectively. For the MSKCC-IMPACT dataset, the cutoff used for hypermutation (13.8 mutations per Mb) was previously determined17. The frequency of hypermutation was similar in the three datasets (85 (5.2%) in DFCI-Profile; 29 (5.3%) in MSKCC-IMPACT; 444 (5.5%) in FMI). The median tumour mutation burden (TMB) in the combined datasets was 2.6 mutations per Mb (range, 0.0–781.3). Compared with non-hypermutated gliomas, hypermutated tumours showed atypical patterns of SNVs, consistent with abnormal mutational processes operating in these samples. Bars represent median and interquartile range for each dataset (right). HPI, homopolymer indels.
