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Mechanisms of Disease: The Damaged Genome in HCC

  • Matthew HoareEmail author
Chapter

Abstract

Hepatocellular carcinoma (HCC) is the second largest cause of cancer-related mortality worldwide, due to rising incidence and a lack of effective therapies. Enormous recent progress has been made in trying to understand the complexity of the altered genome in this cancer and the potential this holds for designing the diagnostics and treatments of the future. In this review we summarise recent data investigating the genetic predisposition to HCC development, mechanisms of genome injury in HCC and the findings of large-scale sequencing projects in HCC that have transformed our understanding of the pathogenesis. We will also explore the role of DNA-methylation changes in HCC and how they provide complementary information to coding DNA changes.

Keywords

HCC Hepatocellular carcinoma Cancer genomics Somatic mutations TERT TP53 Wnt/β-catenin pathway Molecular therapy 

Abbreviations

AFP

Alpha-fetoprotein

CNV

Copy number variation

DEN

Diethylnitrosamine

EGF

Epidermal growth factor

HCC

Hepatocellular carcinoma

HH

Hereditary haemochromatosis

HSC

Hepatic stellate cell

LINEs and SINEs

Long and short interspersed nuclear elements

NAFLD

Non-alcoholic fatty liver disease

NGS

Next-generation sequencing

SNP

Single nucleotide polymorphism

SNVs

Single nucleotide variants

Notes

Acknowledgements

MH is supported by a CRUK Clinician Scientist Fellowship (C52489/A19924).

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Authors and Affiliations

  1. 1.Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUK
  2. 2.Department of MedicineUniversity of CambridgeCambridgeUK

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