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

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

Nat Commun. 2018 03 01;9(1):894

Authors: Wang A, Wu L, Lin J, Han L, Bian J, Wu Y, Robson SC, Xue L, Ge Y, Sang X, Wang W, Zhao H

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.

PMID: 29497050 [PubMed - indexed for MEDLINE]

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