Background: Cholangiocarcinoma (CCA) is a diverse group of malignancies arising from the intra- or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome. Extrahepatic cholangiocarcinoma (ECC) accounts for 90% of CCA. However, little is known about the comprehensive genomic alterations of ECC in Chinese population for providing clinical managements especially targeted therapy.
Methods: Comprehensive genomic profiling (CGP) was performed with next generation sequencing panel on paraffin-embedded tumor from a cohort of 80 Chinese ECC patients.
Results: The most frequently altered genes were TP53 (68%), KRAS (46%), SMAD4 (22%), ARID1A (20%) and CDKN2A (19%). Mutual exclusivity was observed between multiple genes including ARID1A:TP53, KRAS:LRP1B and NF2:TP53. Genetic alterations with potential therapeutic implications were identified in 43% of patients. The top three actionable alterations include CDKN2A (n=11), BRAF (n=5) and ERBB2 (n=4). Potentially actionable alterations were mainly enriched in the G1-S transition, homologous recombination repair, MAPK/ERK pathway.
Conclusions: This is the largest data set of ECC cases providing a comprehensive view on genetic alterations in Chinese population which differs significantly from a US cohort, and indicates the potential clinical implications for targeted therapies.
Keywords: Chinese population; Extrahepatic cholangiocarcinoma (ECC); comprehensive genomic profiling (CGP); targeted therapy.
2019 Hepatobiliary Surgery and Nutrition. All rights reserved.