Fig. 1: Mutational spectrum of patients with CCA.

A The tumor mutation burden (TMB) of nonsynonymous mutations (substitutions and indels) between pCCAs (presented in red) and iCCAs (presented in blue). P value was obtained from Wilcoxon rank-sum test. B Summary composition of COSMIC 30 mutation signatures in pCCAs (red) and iCCAs (blue). COSMIC Signature MMR included signatures 6, 15, and 26; Signature liver included signatures 12, 16, and 24; Signature APOBEC included signatures 2 and 13. C Difference of copy number alterations burden (CNAB) no matter amplification or deletion between pCCAs (red) and iCCAs (blue). Wilcoxon rank-sum test was performed to determine the P value. Box plots depicted the median, quartiles and range. The whiskers in box plots extended to the most extreme data point which is no more than 1.5 times IQR. Outliers were identified using upper/lower quartile ±1.5 times IQR. D Cox proportional hazard model adjusted for age, gender, and stage was conducted to obtain HR and P value (n = 348). E, F Prognostic effect of CNAB in all samples. E CNAB in 43 pCCAs. F CNAB in 126 iCCAs. *P < 0.05; **P < 0.01, ***P < 0.001; TMB Tumor mutation burden, CNV Copy number variation, Amp Amplification, Del Deletion.