Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA).To date,molecular mechanisms underlying the co-existence of HCC and iCCA components in a single tumor remain elusive.Here,we show that H-ChC samples contain substantial private mutations from WES analyses,ranging from 33.1 to 86.4%,indicative of substantive intratumor heterogeneity (ITH).However,on the other hand,numerous ubiquitous mutations shared by HCC and iCCA suggest the monoclonal origin of H-ChC.Mutated genes identified herein,e.g.,VCAN,ACVR2A,and FCGBP,are speculated to contribute to distinct differentiation of HCC and iCCA within H-ChC.Moreover,immunohistochemistry demonstrates that EpCAM is highly expressed in 80% of H-ChC,implying the stemness of such liver cancer.In summary,our data highlight the monoclonal origin and stemness of H-ChC,as well as substantial intratumoral heterogeneity.
Asthma IgE FcεR1-/-Hypotension
Anqiang Wang Liangcai Wu Jianzhen Lin Longzhe Han Jin Bian Yan Wu Simon C.Robson Lai Xue Yunxia Ge Xinting Sang Wenze Wang Haitao Zhao
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Scien Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Scien Department of Pathology, Yanbian University Hospital, Yanji, 133000 China Liver Center and The Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Cen Department of Surgery, The University of Chicago Medicine, Chicago, 60637 USA Novogene Bioinformatics Technology Co., Ltd, Beijing, 100083 China Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences