Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma
Zhao, HaitaoNote: Order does not necessarily reflect citation order of authors.
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CitationWang, 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.
AbstractHepatocellular-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.
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