Figure 6.

CDH13 insertion variation. A, CDH13 enhancer loci at chromosome 16. The top shows the hierarchical TAD boundaries in the lung tissue within the locus 82.6 Mb to 83.3 Mb in chromosome 16. The next is the zoomed-in version between chr16: 82.6 Mb to 82.8 Mb, showing the location of the CDH13 promoter (salmon) and enhancers associated with CDH13 (dark cyan). The next shows the enhancer of interest (chr16:82.6718Mb–82.6728Mb) with enhancer mutations (red lollipop)—the height of the lollipop reflects the number of mutations found across the patient cohort. The last shows the enhancer cores in blue, with the most mutated enhancer core (CIEN-core) in dark blue. B, CIEN-Ins and patient clinical information. Co-mutation plot shows CDH13 expression [log₂(TPM+1)], CIEN-Ins, presence of CIEN-Ins in tumor tissue, presence of CIEN-Ins in matched normal, source of normal (blood or tissue), copy-number variation (CNV; as neutral N, loss L, and gain G), exon mutation (number of mutations), promoter methylation (beta values), TNM staging of cancer, sex of the patient, and the lung cancer subtype are represented by indicated colors in the legend on the right. C,CDH13 expression upon CIEN-Ins deletion. CDH13 gene expression relative to β-actin in wild-type and homozygous deletion of CIEN-Ins in NCI-H460 cell line. The dots represent biological replicates (n = 5). D, Progression-free survival interval probability in lung cancer samples (LUAD+LUSC). E, Disease-free survival interval (DFI) probability in lung cancer samples. F, DFI probability in LUSC samples. For the survival analysis, patients were stratified on the basis of the presence of CIEN-Ins in the tumor, and Kaplan–Meier curves were plotted for the two groups. The risk table with the number of patients is described at the bottom. Differences between the two groups were evaluated using a log‐rank test.