Figure 1

Targeting passenger single-nucleotide variants (SNVs) in haploinsufficient or essential genes is an attractive strategy for CRISPR/Cas9-mediated cancer gene therapy. (a) The number of passenger SNVs and oncogene hotspot mutations in each patient in The Cancer Genome Atlas (TCGA) dataset by 16 cancer types (BLCA, BRCA, COAD, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, OV, PAAD, PRAD, READ, STAD, UCEC). Violin plots represent the density distributions. (b) The number of essential and haploinsufficient genes and oncogenes in human genome. (c) Schematic of CRISPR/Cas9-mediated cancer gene therapy by targeting tumor cell-specific passenger SNVs in haploinsufficient or essential genes. (d) Flowchart depicting the generation of actionable single-guide RNAs (sgRNAs) targeting passenger SNVs in haploinsufficient or essential genes. (e) Density plot comparing the allele frequencies of selected passenger SNVs in haploinsufficient or essential genes (red) and oncogene hotspot mutations (blue). The allele frequency of the entire set of SNVs in haploinsufficient or essential genes before selection is shown in grey. (f) The number of selected passenger SNVs in 16 TCGA cancer types after each step of d and the final number of applicable patients. (g) Venn diagram illustrating the percentage of eligible patients using this method compared to oncogene hotspot mutations among 16 TCGA cancer types. An applicable patient was defined as one with at least one available qualified sgRNA.