Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma

Anqiang Wang, Liangcai Wu, Jianzhen Lin, Longzhe Han, Jin Bian, Yan Wu, Simon C. Robson, Lai Xue, Yunxia Ge, Xinting Sang (), Wenze Wang () and Haitao Zhao ()
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Anqiang Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Liangcai Wu: Chinese Academy of Medical Sciences and Peking Union Medical College
Jianzhen Lin: Chinese Academy of Medical Sciences and Peking Union Medical College
Longzhe Han: Yanbian University Hospital
Jin Bian: Chinese Academy of Medical Sciences and Peking Union Medical College
Yan Wu: Harvard Medical School
Simon C. Robson: Harvard Medical School
Lai Xue: The University of Chicago Medicine
Yunxia Ge: Novogene Bioinformatics Technology Co., Ltd
Xinting Sang: Chinese Academy of Medical Sciences and Peking Union Medical College
Wenze Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Haitao Zhao: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03276-y

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