Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

  1. Mao Mao1,10,14
  1. 1Pfizer Oncology, San Diego, California 92121, USA;
  2. 2BGI-Shenzhen, Shenzhen 518083, China;
  3. 3Department of Biology, University of Copenhagen, Copenhagen, Denmark;
  4. 4Eli Lilly and Company, Indianapolis, Indiana 46285, USA;
  5. 5Merck Research Laboratories, Boston, Massachusetts 02115, USA;
  6. 6Department of Surgery, University of Hong Kong, Hong Kong, China;
  7. 7School of Computing, National University of Singapore, Singapore 117417;
  8. 8The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;
  9. 9King Abdulaziz University, Jeddah, Saudi Arabia;
  10. 10Asian Cancer Research Group, Inc., Wilmington, Delaware 19808, USA;
  11. 11Departments of Pharmacology and Surgery, National University of Singapore, Singapore 117597;
  12. 12Institute of Molecular and Cell Biology, A*STAR, Singapore 138673

    1. ↵13 These authors contributed equally to this work.

    Abstract

    Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.

    Footnotes

    • ↵14 Corresponding authors

      E-mail liyr{at}genomics.org.cn

      E-mail jmluk{at}hku.hk

      E-mail mao_m{at}yahoo.com

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.154492.113.

      Freely available online through the Genome Research Open Access option.

    • Received January 4, 2013.
    • Accepted June 17, 2013.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

    | Table of Contents
    OPEN ACCESS ARTICLE

    This Article

    1. Published in Advance June 20, 2013, doi: 10.1101/gr.154492.113 Genome Res. 23: 1422-1433 © 2013, Published by Cold Spring Harbor Laboratory Press

    Article Category

    Share

    Preprint Server



    Current Issue

    1. March 2024, 34 (3)
    1. Current Issue
    1. Alert me to new issues of Genome Research