Fig. 2. IDH1/2 mutations by variant, glioma category, and type of screening.

(a) In a pooled analysis of over 3400 gliomas from 37 studies in which mutation subtypes were reported, R132H was the most common IDH1 variant, comprising 92% of all IDH1 mutations (P < 0.0001). The rarest was R132P, occurring in a single case [54]. (b) In contrast, there was less preference for a specific type of IDH2 mutation, though the R172K variant was present in 60% of IDH2-mutant tumors (P < 0.0001, N = 89). (c) Inter-study mutation frequencies significantly differ in grades II-III astrocytomas and grade III oligodendrogliomas, depending on whether the studies tested for both IDH1 and IDH2 mutations (red bars, N = 4324 gliomas from 26 studies), screened for just IDH1 mutations (purple bars, N = 2075 gliomas from 12 studies), or only used the R132H IDH1 antibody (blue bars, N = 794 gliomas from 6 studies). Not enough oligodendroglial tumors have been interrogated with R132H IDH1 antibody to be reliably compared with the other columns. Of note, mean mutation frequencies in IDH1-only studies sometimes barely exceeded the frequencies reported in IDH1/2 papers (purple versus red bars in AII and sGBM subgroups). This apparent incongruity can be explained by inter-cohort variations, especially given how rare IDH2 mutations are in astrocytic tumors (see Figure 4). A list of the studies from which these data are derived is in Supplemental Table 1. All data bars in a-c represent mean ± SEM; statistical analyses were done via Student's t-test or ANOVA with Kruskal-Wallis post hoc test, as appropriate. *P < 0.05; **P < 0.01; ***P < 0.001. AII = grade II diffuse astrocytoma; AIII = grade III anaplastic astrocytoma; pGBM = primary GBM; sGBM = secondary GBM; OII = grade II oligodendroglioma; OIII = grade III anaplastic oligodendroglioma; OAII = grade II oligoastrocytoma; OAIII = grade III anaplastic oligoastrocytoma.