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Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma
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 rema...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832792/ https://www.ncbi.nlm.nih.gov/pubmed/29497050 http://dx.doi.org/10.1038/s41467-018-03276-y |
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author | Wang, Anqiang Wu, Liangcai Lin, Jianzhen Han, Longzhe Bian, Jin Wu, Yan Robson, Simon C. Xue, Lai Ge, Yunxia Sang, Xinting Wang, Wenze Zhao, Haitao |
author_facet | Wang, Anqiang Wu, Liangcai Lin, Jianzhen Han, Longzhe Bian, Jin Wu, Yan Robson, Simon C. Xue, Lai Ge, Yunxia Sang, Xinting Wang, Wenze Zhao, Haitao |
author_sort | Wang, Anqiang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5832792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58327922018-03-05 Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma Wang, Anqiang Wu, Liangcai Lin, Jianzhen Han, Longzhe Bian, Jin Wu, Yan Robson, Simon C. Xue, Lai Ge, Yunxia Sang, Xinting Wang, Wenze Zhao, Haitao Nat Commun Article 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. Nature Publishing Group UK 2018-03-01 /pmc/articles/PMC5832792/ /pubmed/29497050 http://dx.doi.org/10.1038/s41467-018-03276-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Anqiang Wu, Liangcai Lin, Jianzhen Han, Longzhe Bian, Jin Wu, Yan Robson, Simon C. Xue, Lai Ge, Yunxia Sang, Xinting Wang, Wenze Zhao, Haitao Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
title | Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
title_full | Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
title_fullStr | Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
title_full_unstemmed | Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
title_short | Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
title_sort | whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832792/ https://www.ncbi.nlm.nih.gov/pubmed/29497050 http://dx.doi.org/10.1038/s41467-018-03276-y |
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