Fig 4.

Evidence for ordered appearance of aberrations in isocitrate dehydrogenase 1 (IDH1) mutant glioblastoma (GBM). (A) Top: Frequencies of sequences found at IDH1^R132 show that the predominant substitution is His (yellow box). Bottom: Among gliomas with mutations at IDH1^R132 (IDH1MUT) and p53^R273, a predominance of Cys substitution at p53^R273 is seen (yellow box); for IDH1^R132-wild type (IDH1WT) tumors, the preferred substitution at p53^R273 is His. (B) Schematic diagram showing that IDH1 mutation on the template strand and p53 mutation on coding strand can select for the expression of IDH1 mutant protein before p53 mutant protein if replication is delayed.