Figure 1. Multiplatform genetic analysis of UTUC.

(A) Mutational burden (blue) and their variability (red) in 199 UTUC samples (top) with mutation status of MMR genes, and history of cancer (bottom) for hypermutated samples. (B) Four predominant SBS signatures (left) and strand bias for each signature (right) in non-hypermutated UTUC samples. (C) Box plots of SNVs assigned to Sig. D, according to the allelic status of ALDH2 (rs 671) and history of alcohol consumption (left) and forest plots of odds ratios for indicated risk factors with 95% confidence intervals (CIs; right). P values calculated by two-sided Mann-Whitney U test with Bonferroni correction. The median, first and third quartiles, as well as outliners, are indicated with whiskers extending to the furthest value within 1.5 of the interquartile range in box plots. **P < 0.01, ***P < 0.001. (D and E) Comparisons of frequency of common genetic lesions (left), between invasive UBC (n = 375) and UTUC (n = 81) (D) and ureter (n = 54) and renal pelvis (n = 112) cancers (E). Log₂-transformed odds ratios are also shown with 95% CIs (right). Significant enrichment is shown by asterisks (q < 0.1, two-sided Fisher’s exact test with Benjamini-Hochberg adjustment for multiple testing). TERT p., TERT promoter. (F) Summary of the molecular features in urothelial cancers according to tumor location. MSI, microsatellite instability.

See also Figures S1–S3 and Tables S2 and S3.