Tumor mutation burden (TMB) and individual gene mutations in derivative PDX. (A) TMB gain (relative to matched parental PDX) in derivative PDX with intact DNA mismatch repair (MMR) genes compared to derivative PDX with DNA MMR gene mutations (mut/Mb = mutations per megabase, ** p < 0.05). (B) TMB gain in derivative PDX with intact DNA MMR genes compared to derivative PDX with a single MMR gene mutation and two or more MMR gene mutations (**** p < 0.0001). (C) Heat map of the 35 most frequently mutated genes in PDX derivatives treated with TMZ (* TMZ ×1, ** RT+TMZ ×1, † RT+TMZ ×2, ‡ RT+TMZ ×3, ‡‡ TMZ ×4). (D) Scatterplot illustrating the frequency of protein-coding mutations in genes as a function of gene coding sequence (CDS) length in base pairs (bp). TTN has the longest CDS among human genes and was the most frequently mutated in post-TMZ PDX (* p < 0.05). (E) Frequency of protein-coding mutations as a function of CDS length, with TTN eliminated (* p < 0.05). (F) Heat map of the 15 most frequently mutated genes in PDX derivatives treated with only radiation therapy (RT). (G) Frequency of protein-coding mutations as a function of CDS length in PDX derivatives treated with only RT.