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Exploration of liver cancer genomes

Nature Reviews Gastroenterology & Hepatology volume 11, pages 340–349 (2014)Cite this article

Subjects

Key Points

  • Whole-exome and whole-genome sequencing have provided a comprehensive and high-resolution view of somatic genomic alterations in liver cancer

  • Global epigenetic analyses have further identified both unique and complementary molecular alterations in liver cancer

  • Somatic mutational signatures of the liver cancer genome are complex and tend to be associated with epidemiological backgrounds

  • Integration of genetic and epigenetic alteration profiles has elucidated core oncogenic pathways, potential therapeutic targets and new molecular classifications in liver cancer

Abstract

Liver cancer is the third leading cause of cancer-related death worldwide. Advances in sequencing technologies have enabled the examination of liver cancer genomes at high resolution; somatic mutations, structural alterations, HBV integration, RNA editing and retrotransposon changes have been comprehensively identified. Furthermore, integrated analyses of trans-omics data (genome, transcriptome and methylome data) have identified multiple critical genes and pathways implicated in hepatocarcinogenesis. These analyses have uncovered potential therapeutic targets, including growth factor signalling, WNT signalling, the NFE2L2-mediated oxidative pathway and chromatin modifying factors, and paved the way for new molecular classifications for clinical application. The aetiological factors associated with liver cancer are well understood; however, their effects on the accumulation of somatic changes and the influence of ethnic variation in risk factors still remain unknown. The international collaborations of cancer genome sequencing projects are expected to contribute to an improved understanding of risk evaluation, diagnosis and therapy for this cancer.

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Figure 1: Multiple aetiological factors and ethnic differences affect somatic mutation signatures in liver cancer.
Figure 2: Core oncogenic pathways in hepatocarcinogenesis.

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Acknowledgements

We apologize for the many excellent works which are not acknowledged in the reference list owing to the limited space. The work of the authors is supported partially by Grants-in-Aid from the Ministry of Health, Labour and Welfare for the 3rd-term Comprehensive 10-year Strategy for Cancer Control, National Cancer Center Research and Development Fund (23-A-8) (T. Shibata), and JSPS KAKENHI Grant Number 24221011 (A. Aburatani).

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  1. Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, 104-0045, Chuo-ku, Japan

    Tatsuhiro Shibata

  2. Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1, Komaba, Tokyo, 153-8904, Meguro-ku, Japan

    Hiroyuki Aburatani

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  1. Tatsuhiro Shibata
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  2. Hiroyuki Aburatani
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Both authors contributed equally to all aspects of this manuscript.

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Correspondence to Tatsuhiro Shibata.

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The authors declare no competing financial interests.

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Shibata, T., Aburatani, H. Exploration of liver cancer genomes. Nat Rev Gastroenterol Hepatol 11, 340–349 (2014). https://doi.org/10.1038/nrgastro.2014.6

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