(A) Mean fold-change of expression (CRC/crypts) of genes associated with gained enhancers containing indels (grey; n = 352 sample-gene pairs) versus the same genes in cell lines with gained enhancers but lacking indels (black; n = 2384 sample-gene pairs). *p<0.01, 2-sample t-test (Figure 3—source data 1). (B) Enriched GO terms associated with enhancer indel genes. (C) (black) Distribution of number of TCGA samples with recurrent indel and (grey) average recurrence distribution from random sampling of TCGA indels (p<0.05, χ2 test). Listed genes have indels recurrent in three or more TCGA samples. Pie chart shows fraction of enhancer indels that are recurrent in at least one primary CRC tumor (Figure 3—source data 2). (D) Enriched GO terms associated with recurrent enhancer indel genes. (E). Distribution of dependency scores in HCT-116 cells for all expressed genes (grey; n = 13,584), indel genes (red; n = 100), recurrent indel genes (dotted-red; n = 17), and recurrent indel genes with ‘Cell Proliferation’ annotation (dotted-blue; n = 5). *p<0.05 for ‘Cell Proliferation’ recurrent indel gene versus all expressed genes, Wilcox ranksum test. (F) Genes ranked by dependency scores, showing select oncogenes (black circles), and recurrent indel genes with (red circles) and without (blue circles) enhancer mutation in HCT-116 cells. Data for recurrent indel genes shown in ‘C’ (USP8, AP4E1, MRPS22) were not available.