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Nat Rev Cancer. 2015 Nov;15(11):653-67. doi: 10.1038/nrc4017.

Functional and genetic deconstruction of the cellular origin in liver cancer.

Author information

1
Department of Medicine I, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany.
2
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maal√łes Vej 5, 2200 Copenhagen N, Denmark.
3
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.

PMID:
26493646
DOI:
10.1038/nrc4017
[Indexed for MEDLINE]

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