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

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.

journal_name

Nat Commun

journal_title

Nature communications

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

doi

10.1038/s41467-018-03276-y

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

894

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03276-y

journal_volume

9

pub_type

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