Skip to main content
SpringerLink
Log in

Genomics Studies in Hepatocellular Carcinoma via Next-Generation Sequencing

  • Chapter
  • First Online:
Book cover Precision Molecular Pathology of Liver Cancer

Part of the book series: Molecular Pathology Library ((MPLB))

Abstract

Hepatocellular carcinoma (HCC), a major type of liver cancer, is a clinically and biologically heterogeneous malignancy. Recent advances in next-generation sequencing (NGS), a massively parallel nucleotide sequencing technology, allow researchers for cost-effective and simultaneous identification of genetic alterations, transcriptomic changes at much greater sensitivity, and accuracy. A large scale of mutational screening, gene expression examination, and their integration via NGS have been done in HCCs. These studies may enable the identification of new HCC genetic drivers and provide clues for HCC treatment using molecular-targeted therapies. The recent HCC NGS studies in this decade and their potential clinical utilization, with a focus on HCC heterogeneity, are discussed in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6:674–87.

    Article  CAS  PubMed  Google Scholar 

  2. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 2002;31:339–46.

    Article  CAS  PubMed  Google Scholar 

  3. Llovet JM, et al. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.

    Article  PubMed  Google Scholar 

  4. Lozano R, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–128.

    Article  PubMed  Google Scholar 

  5. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–73.e1.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Arzumanyan A, et al. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 2013;13:123–35.

    Article  CAS  PubMed  Google Scholar 

  7. Pujol FH, et al. Worldwide genetic diversity of HBV genotypes and risk of hepatocellular carcinoma. Cancer Lett. 2009;286:80–8.

    Article  CAS  PubMed  Google Scholar 

  8. Forner A, et al. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.

    Article  PubMed  Google Scholar 

  9. Levrero M. Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene. 2006;25:3834–47.

    Article  CAS  PubMed  Google Scholar 

  10. Fattovich G, et al. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35–50.

    Article  PubMed  Google Scholar 

  11. Romeo R, et al. High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in patients with chronic hepatitis delta. PLoS One. 2014;9:e92062.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Boffetta P, Hashibe M. Alcohol and cancer. Lancet Oncol. 2006;7:149–56.

    Article  CAS  PubMed  Google Scholar 

  13. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.

    Article  CAS  PubMed  Google Scholar 

  14. Hartling L, et al. Association between alcohol consumption and cancers in the Chinese population—a systematic review and meta-analysis. PLoS One. 2011;6:e18776.

    Article  CAS  Google Scholar 

  15. Baffy G, et al. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56:1384–91.

    Article  PubMed  Google Scholar 

  16. Nobili V, et al. A 360-degree overview of paediatric NAFLD: recent insights. J Hepatol. 2013;58:1218–29.

    Article  PubMed  Google Scholar 

  17. Calle EE, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med. 2003;348:1625–38.

    Article  PubMed  Google Scholar 

  18. Larsson S, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007;97:1005–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Arase Y, et al. Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C. Hepatology. 2013;57:964–73.

    Article  CAS  PubMed  Google Scholar 

  20. Hsiang JC, et al. Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients. J Gastroenterol Hepatol. 2015;30:591–9.

    Article  CAS  PubMed  Google Scholar 

  21. Lai MS, et al. Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection. Hepatology. 2006;43:1295–302.

    Article  PubMed  Google Scholar 

  22. Feitelson MA, et al. Genetic mechanisms of hepatocarcinogenesis. Oncogene. 2002;21:2593–604.

    Article  CAS  PubMed  Google Scholar 

  23. Nault JC, Zucman-Rossi J. Genetics of hepatocellular carcinoma: the next generation. J Hepatol. 2014;60:224–6.

    Article  CAS  PubMed  Google Scholar 

  24. Roncalli M, et al. Histopathological classification of hepatocellular carcinoma. Dig Liver Dis. 2010;42(Suppl 3):S228–34.

    Article  PubMed  Google Scholar 

  25. Severi T, et al. Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets. Acta Pharmacol Sin. 2010;31:1409–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Park JW, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015;35:2155–66.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Villanueva A, et al. Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis, and therapy. Annu Rev Med. 2010;61:317–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bruix J, et al. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–9.

    Article  CAS  PubMed  Google Scholar 

  29. Yau T, et al. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146:1691–700.e3.

    Article  PubMed  Google Scholar 

  30. Kudo M, et al. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol. 2003;38:207–15.

    Article  PubMed  Google Scholar 

  31. Okuda K, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56:918–28.

    Article  CAS  PubMed  Google Scholar 

  32. Forner A, et al. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol. 2014;11:525–35.

    Article  CAS  PubMed  Google Scholar 

  33. Quetglas IM, et al. Integration of genomic information in the clinical management of HCC. Best Pract Res Clin Gastroenterol. 2014;28:831–42.

    Article  CAS  PubMed  Google Scholar 

  34. Budhu A, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology. 2008;47:897–907.

    Article  CAS  PubMed  Google Scholar 

  35. Budhu A, et al. Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes. Gastroenterology. 2013;144:1066–75.e1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ji J, Wang XW. New kids on the block: diagnostic and prognostic microRNAs in hepatocellular carcinoma. Cancer Biol Ther. 2009;8:1686–93.

    Article  PubMed  Google Scholar 

  37. Ji J, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;50:472–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ji J, et al. Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol. 2010;52:690–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ji J, et al. Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma. Hepatology. 2015;62:829–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kim JW, et al. Cancer-associated molecular signature in the tissue samples of patients with cirrhosis. Hepatology. 2004;39:518–27.

    Article  CAS  PubMed  Google Scholar 

  41. Lee JS, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004;40:667–76.

    Article  CAS  PubMed  Google Scholar 

  42. Yamashita T, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136:1012–24.

    Article  CAS  PubMed  Google Scholar 

  43. Ye QH, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med. 2003;9:416–23.

    Article  CAS  PubMed  Google Scholar 

  44. Parpart S, et al. Modulation of miR-29 expression by alpha-fetoprotein is linked to the hepatocellular carcinoma epigenome. Hepatology. 2014;60:872–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Honda M, et al. Differential gene expression between chronic hepatitis B and C hepatic lesion. Gastroenterology. 2001;120:955–66.

    Article  CAS  PubMed  Google Scholar 

  46. Hashimoto K, et al. Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH. Mod Pathol. 2004;17:617–22.

    Article  CAS  PubMed  Google Scholar 

  47. Huang J, et al. Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus-associated hepatocellular carcinoma. FEBS Lett. 2006;580:3571–81.

    Article  CAS  PubMed  Google Scholar 

  48. Boyault S, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology. 2007;45:42–52.

    Article  CAS  PubMed  Google Scholar 

  49. Zucman-Rossi J, et al. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology. 2015;149:1226–39.e4.

    Article  CAS  PubMed  Google Scholar 

  50. Yamashita T, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 2008;68:1451–61.

    Article  CAS  PubMed  Google Scholar 

  51. Ji J, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361:1437–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ji J, et al. Development of a miR-26 companion diagnostic test for adjuvant interferon-alpha therapy in hepatocellular carcinoma. Int J Biol Sci. 2013;9:303–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Margulies M, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature. 2005;437:376–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Eid J, et al. Real-time DNA sequencing from single polymerase molecules. Science. 2009;323:133–8.

    Article  CAS  PubMed  Google Scholar 

  55. Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11:31–46.

    Article  CAS  PubMed  Google Scholar 

  56. Rothberg JM, Leamon JH. The development and impact of 454 sequencing. Nat Biotechnol. 2008;26:1117–24.

    Article  CAS  PubMed  Google Scholar 

  57. Ronaghi M, et al. Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem. 1996;242:84–9.

    Article  CAS  PubMed  Google Scholar 

  58. Feng YJ, et al. Parallel tagged amplicon sequencing of relatively long PCR products using the Illumina HiSeq platform and transcriptome assembly. Mol Ecol Resour. 2016;16:91–102.

    Article  CAS  PubMed  Google Scholar 

  59. Jeon YS, et al. Improved pipeline for reducing erroneous identification by 16S rRNA sequences using the Illumina MiSeq platform. J Microbiol. 2015;53:60–9.

    Article  CAS  PubMed  Google Scholar 

  60. Morozova O, Marra MA. Applications of next-generation sequencing technologies in functional genomics. Genomics. 2008;92:255–64.

    Article  CAS  PubMed  Google Scholar 

  61. Cloonan N, et al. Stem cell transcriptome profiling via massive-scale mRNA sequencing. Nat Methods. 2008;5:613–9.

    Article  CAS  PubMed  Google Scholar 

  62. Valouev A, et al. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res. 2008;18:1051–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Quail MA, et al. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics. 2012;13:341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Schadt EE, et al. A window into third-generation sequencing. Hum Mol Genet. 2010;19:R227–40.

    Article  CAS  PubMed  Google Scholar 

  65. Buermans HP, den Dunnen JT. Next generation sequencing technology: advances and applications. Biochim Biophys Acta. 2014;1842:1932–41.

    Article  CAS  PubMed  Google Scholar 

  66. Wheeler DA, et al. The complete genome of an individual by massively parallel DNA sequencing. Nature. 2008;452:872–6.

    Article  CAS  PubMed  Google Scholar 

  67. Meyerson M, et al. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11:685–96.

    Article  CAS  PubMed  Google Scholar 

  68. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26:1135–45.

    Article  CAS  PubMed  Google Scholar 

  69. Brechot C, et al. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature. 1980;286:533–5.

    Article  CAS  PubMed  Google Scholar 

  70. Fujimoto A, et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat Genet. 2012;44:760–4.

    Article  CAS  PubMed  Google Scholar 

  71. Paterlini-Brechot P, et al. Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene. 2003;22:3911–6.

    Article  CAS  PubMed  Google Scholar 

  72. Sung WK, et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet. 2012;44:765–9.

    Article  CAS  PubMed  Google Scholar 

  73. Toh ST, et al. Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations. Carcinogenesis. 2013;34:787–98.

    Article  CAS  PubMed  Google Scholar 

  74. Li W, et al. HIVID: an efficient method to detect HBV integration using low coverage sequencing. Genomics. 2013;102:338–44.

    Article  CAS  PubMed  Google Scholar 

  75. Totoki Y, et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat Genet. 2014;46:1267–73.

    Article  CAS  PubMed  Google Scholar 

  76. Pawlotsky JM. Hepatitis C virus population dynamics during infection. Curr Top Microbiol Immunol. 2006;299:261–84.

    CAS  PubMed  Google Scholar 

  77. Park CW, et al. Comparison of quasispecies diversity of HCV between chronic hepatitis c and hepatocellular carcinoma by Ultradeep pyrosequencing. Biomed Res Int. 2014;2014:853076.

    PubMed  PubMed Central  Google Scholar 

  78. Miura M, et al. Deep-sequencing analysis of the association between the quasispecies nature of the hepatitis C virus core region and disease progression. J Virol. 2013;87:12541–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Jiang JH, et al. Clinical significance of the ubiquitin ligase UBE3C in hepatocellular carcinoma revealed by exome sequencing. Hepatology. 2014;59:2216–27.

    Article  CAS  PubMed  Google Scholar 

  80. Guichard C, et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 2012;44:694–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Jhunjhunwala S, et al. Diverse modes of genomic alteration in hepatocellular carcinoma. Genome Biol. 2014;15:436.

    PubMed  PubMed Central  Google Scholar 

  82. Schulze K, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015;47:505–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Forbes SA, et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 2011;39:D945–50.

    Article  CAS  PubMed  Google Scholar 

  84. Forbes SA, et al. COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res. 2010;38:D652–7.

    Article  CAS  PubMed  Google Scholar 

  85. Cleary SP, et al. Identification of driver genes in hepatocellular carcinoma by exome sequencing. Hepatology. 2013;58:1693–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Li M, et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet. 2011;43:828–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lin KT, et al. Identification of latent biomarkers in hepatocellular carcinoma by ultra-deep whole-transcriptome sequencing. Oncogene. 2014;33:4786–94.

    Article  CAS  PubMed  Google Scholar 

  88. Kan Z, et al. Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma. Genome Res. 2013;23:1422–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Marquardt JU, et al. Sequential transcriptome analysis of human liver cancer indicates late stage acquisition of malignant traits. J Hepatol. 2014;60:346–53.

    Article  CAS  PubMed  Google Scholar 

  90. Fernandez-Banet J, et al. Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma. Genomics. 2014;103:189–203.

    Article  CAS  PubMed  Google Scholar 

  91. Xu H, et al. Non-invasive analysis of genomic copy number variation in patients with hepatocellular carcinoma by next generation DNA sequencing. J Cancer. 2015;6:247–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Chen Y, et al. Exome capture sequencing reveals new insights into hepatitis B virus-induced hepatocellular carcinoma at the early stage of tumorigenesis. Oncol Rep. 2013;30:1906–12.

    Article  CAS  PubMed  Google Scholar 

  93. Meerzaman DM, et al. Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma. Cancer Genomics Proteomics. 2014;11:1–12.

    PubMed  Google Scholar 

  94. Murakami Y, et al. Comparison of hepatocellular carcinoma miRNA expression profiling as evaluated by next generation sequencing and microarray. PLoS One. 2014;9:e106314.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Wojcicka A, et al. Next generation sequencing reveals microRNA isoforms in liver cirrhosis and hepatocellular carcinoma. Int J Biochem Cell Biol. 2014;53:208–17.

    Article  CAS  PubMed  Google Scholar 

  96. Law PT, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013;58:1165–73.

    Article  CAS  PubMed  Google Scholar 

  97. Selitsky SR, et al. Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C. Sci Rep. 2015;5:7675.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Merrick BA, et al. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats. PLoS One. 2013;8:e61768.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Yang W, et al. Genome-wide miRNA-profiling of aflatoxin B1-induced hepatic injury using deep sequencing. Toxicol Lett. 2014;226:140–9.

    Article  CAS  PubMed  Google Scholar 

  100. Chan KC, et al. Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc Natl Acad Sci U S A. 2013;110:18761–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Shen J, et al. Integrative epigenomic and genomic filtering for methylation markers in hepatocellular carcinomas. BMC Med Genet. 2015;8:28.

    Google Scholar 

  102. Janku F, et al. Identification of novel therapeutic targets in the PI3K/AKT/mTOR pathway in hepatocellular carcinoma using targeted next generation sequencing. Oncotarget. 2014;5:3012–22.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Kelley RK, et al. Circulating tumor cells in hepatocellular carcinoma: a pilot study of detection, enumeration, and next-generation sequencing in cases and controls. BMC Cancer. 2015;15:206.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Ouyang L, et al. Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas. BMC Med Genet. 2014;7:2.

    Google Scholar 

  105. Chapman PB, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Chapman PB, et al. Frontline approach to metastatic BRAF-mutant melanoma diagnosis, molecular evaluation, and treatment choice. Am Soc Clin Oncol Educ Book. 2014;34:e412–21.

    Article  Google Scholar 

  107. Kwak EL, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Llovet JM, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  PubMed  Google Scholar 

  109. Totoki Y, et al. High-resolution characterization of a hepatocellular carcinoma genome. Nat Genet. 2011;43:464–9.

    Article  CAS  PubMed  Google Scholar 

  110. Ding D, et al. Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. PLoS Genet. 2012;8:e1003065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Huang J, et al. Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. Nat Genet. 2012;44:1117–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China

    Xiyang Wei Ph.D., Niya Liu Ph.D. & Junfang Ji Ph.D.

  2. Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA

    Xin Wei Wang M.D., Ph.D.

Authors
  1. Xiyang Wei Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Niya Liu Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Wei Wang M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junfang Ji Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junfang Ji Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School and New Jersey Medical School, Newark, New Jersey, USA

    Chen Liu

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Wei, X., Liu, N., Wang, X.W., Ji, J. (2018). Genomics Studies in Hepatocellular Carcinoma via Next-Generation Sequencing. In: Liu, C. (eds) Precision Molecular Pathology of Liver Cancer. Molecular Pathology Library. Springer, Cham. https://doi.org/10.1007/978-3-319-68082-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-68082-8_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-68080-4

  • Online ISBN: 978-3-319-68082-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation