Comprehensive molecular characterization of Chinese patients with intrahepatic and extrahepatic cholangiocarcinoma.

Abstract

e16128 Background: Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. Therefore, understanding the molecular characteristics of Chinese CCA patients is helpful for individualized treatment of patients. Methods: We reviewed 397 Chinese cholangiocarcinoma patients, including 125 extrahepatic and 272 intrahepatic, with paired tumor-normal samples sequenced by a 1021 gene panel. Tumor mutational burden(TMB) was defined as the number of somatic non-synonymous mutations per megabase of the panel region. Results: The genomic profiling was analyzed and indicated that TP53 and KRAS were the most frequently mutated gene, which were detected in 47% and 27% samples. The common targets gene of FGFR2 and IDH1 were detected in 6% and 4% patients in our cohort. Meanwhile, the prevalence of gene mutated was compared between intrahepatic and extrahepatic cholangiocarcinoma. The TP53 mutation was more frequently prevalence in intrahepatic cholangiocarcinoma (51% vs 36%, p = 0.0048); and the FGFR2 fusion more detected in extrahepatic cholangiocarcinoma (4% vs 10%, p = 0.0214). The TMB was also analyzed in our study and ranged from 1 to 194 (median:5). No difference was found between intrahepatic and extrahepatic cholangiocarcinoma in TMB. Besides, the TP53 mutations showed significant association with higher TMB (p < 0.0001), both intrahepatic and extrahepatic cholangiocarcinoma; and KRAS mutations showed significant association with higher TMB (p = 0.029) in intrahepatic cholangiocarcinoma. Interesting, KRAS mutations was also association with TMB in extrahepatic cholangiocarcinoma; The KRAS-mutated & TP53-wildtype(wt) patients showed higher TMB than double-wt patients (5.5 vs 4, p = 0.048) and the only TP53-mutated patients showed higher TMB than double-mutated patients (8 vs 6, p = 0.047). Conclusions: In conclusion, the genomic profiling and molecular characterization were difference between intrahepatic and extrahepatic cholangiocarcinoma, which may helpful in clinical diagnosis and treatment.