Review of Genetic and Epigenetic Alterations in Hepatocarcinogenesis

doi: 10.2174/138920211795564359.

Genetic and epigenetic signatures in homo hepatocellular carcinoma: a systematic review

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• PMID: 21966251
• PMCID: PMC3129047
• DOI: 10.2174/138920211795564359

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Genetic and epigenetic signatures in human hepatocellular carcinoma: a systematic review

Naoshi Nishida  et al. Curr Genomics. 2011 April .

Costless PMC article

Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide, and the incidence of this fatal disease is all the same on rise. The majority of HCCs sally in the groundwork of a chronic liver disease, such as chronic hepatitis and liver cirrhosis. The current understanding is that majority of HCCs evolve as a consequence of chronic inflammation and due to the presence of infection with hepatitis viruses. These underlying pathogenic stimuli later induce a spectrum of genetic and epigenetic alterations in several cancer-related genes, which are involved in cell-cycle regulation, jail cell growth and adhesion. Such widespread genomic alterations crusade disruption of normal cellular signaling and finally pb to the acquisition of a malignant phenotype in HCC. In general, the type of gene alterations, such as point mutations, deletion of chromosomal regions and abnormal methylation of cistron promoters differ according to the private targeted gene. In HCC, incidence of genetic alterations is relatively rare and is express to a subset of few cancer-specific genes, such every bit the tumor suppressor p53, RB genes and oncogenes such every bit the CTNNB1. In dissimilarity, epigenetic changes that involve aberrant methylation of genes and other post-transcriptional histone modifications occur far more often, and some of these epigenetic alterations are now existence exploited for the development of molecular diagnostic signatures for HCC. In addition, recent findings of unique microRNA expression profiles as well provide an testify for the existence of novel mechanisms for factor expression regulation in HCC. In this review article, we will review the current land of knowledge on the activation of various oncogenic pathways and the inactivation of tumor suppressor pathways in HCC that event in the disruption of cancer-related gene office. In addition, we will specifically emphasize the clinical implication of some of these genetic and epigenetic alterations in the management of hepatocarcinogenesis.

Keywords: DNA methylation; Oncogenic pathway; hepatocellular carcinoma; mutation; oncogene; tumor suppressor gene..

Figures

Fig. (1)

Hateful methylation levels and frequencies of hypermethylation of several tumor suppressor genes (TSGs) in HCC. In contrast to genetic alterations such equally point mutation, a multifariousness of TSGs are frequently inactivated via epigenetic mechanism, suggesting that DNA methylation is a major alteration as a commuter for human hepatocarcinogenesis.

Fig. (two)

Schematic representation of alterations in p53/ARF and RB/INK4A pathways in HCC. Molecules with oncogenic role are shown in yellow and those with tumor suppressive office are shown in blue. Specific type of genetic and epigenetic alterations found in HCC are shown in cherry letter.

Fig. (3)

Schematic representation of Wnt/β-catenin pathway and the alterations reported in HCC. Functions of molecules shown in yellow and blueish represent oncogenic and tumor suppressive respectively. Specific types of genetic and epigenetic alterations found in HCC are shown in scarlet alphabetic character.

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