741PGenomic analysis of hepatobiliary lithiasis associated cholangiocarcinoma revealed a distinct subtype feature

Abstract Background Hepatic stone or lithiasis is a known risk factor for intrahepatic cholangiocarcinoma (ICC) in clinic, however the process and genomic background of the hepatobiliary lithiasis associated cholangiocarcinoma (BCAC) is completely unknown. Methods Here, we retrospectively collected 81 paired intrahepatic cholangiocarcinoma (ICC) frozen cancerous and adjacent tissues including those patients combining biliary calculi. Whole exome sequence (WES, average 400x) and RNA-seq were applied to characterize this cohort. Results Among them, prognosis of 64 patients from 2011 to 2013 revealed that BCAC had poor overall survival (18.6 months vs 28.6 months, P = 0.024, Kaplan-Meier) compared to those of non-stone ICC. WES of 81 ICC patients showed that BCAC displayed a distinct mutation pattern, with EPHA2 and SMAD4 genes significantly enriched in BCAC (P  Conclusions Our results demonstrate that BCAC is a distinct CCAs subtype and biliary calculi might be an independent factor for ICC and result in a poor prognosis. Legal entity responsible for the study BGI-Shenzhen. Funding Shenzhen Science and Technology Innovation Committee. Disclosure All authors have declared no conflicts of interest.