Extended Data Fig. 6: Untreated Hcmel12 and 4334 lineage tumors recapitulate B78-D14 lineage.
a Survival of C57/BL6 mice subcutaneously injected with indicated cells (n = 8–18 animals). b Untreated tumor weight at endpoint (n = 17, 18, 11 and 8 individual tumours). c Survival of C57/BL6 and NSG mice subcutaneously injected with indicated Hcmel12 cells (n = 10 animals). d Untreated tumor weight at endpoint (n = 10 individual tumours). e Change in detected heteroplasmy in bulk tumor samples (n = 14 and 8 individual tumours). 4434 mutant tumors display a modest shift in heteroplasmy that is not seen in Hcmel12 or B78 (Extended Data Fig. 3d), likely reflecting enhanced immunogenicity of the mutant genotype. f Bulk tumor mtDNA copy number (n = 12, 9, 8 and 8 individual tumours). g Heatmap of steady-state abundance of metabolic terminal fumarate adducts, succinylcysteine and succinicGSH, demonstrating that metabolic changes observed in B78 mutant tumors are preserved in Hcmel12 in vivo (n = 9 individual tumours). h GSEA of Hcmel12 bulk tumor RNAseq data (n= 3 individual tumours) showing mutant80% versus wild-type. Log-rank (Mantel-Cox) test (A, C), one-tailed student’s t-test applied (B, D) or two-tailed Wilcoxon signed rank test (H) were applied. Error bars indicate SD. Measure of centrality is mean. * P = < 0.05, ** P = <0.01. Number of replicates are described across conditions from left to right as presented. Heatmap representations of data where asterisks are not present report non-significant changes.
