Wang, AnqiangWu, LiangcaiLin, JianzhenHan, LongzheBian, JinWu, YanRobson, SimonXue, LaiGe, YunxiaSang, XintingWang, WenzeZhao, Haitao2018-04-192018Wang, A., L. Wu, J. Lin, L. Han, J. Bian, Y. Wu, S. C. Robson, et al. 2018. “Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma.” Nature Communications 9 (1): 894. doi:10.1038/s41467-018-03276-y. http://dx.doi.org/10.1038/s41467-018-03276-y.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982096Hepatocellular-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.en-USJournal Article2018-04-1910.1038/s41467-018-03276-y