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‣ Genetic and Epigenetic Signatures in Human Hepatocellular Carcinoma: A Systematic Review

Nishida, Naoshi; Goel, Ajay
Fonte: Bentham Science Publishers Ltd Publicador: Bentham Science Publishers Ltd
Tipo: Artigo de Revista Científica
Publicado em /04/2011 Português
Relevância na Pesquisa
Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide, and the incidence of this fatal disease is still on rise. The majority of HCCs emerge in the background 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 subsequently induce a spectrum of genetic and epigenetic alterations in several cancer-related genes, which are involved in cell-cycle regulation, cell growth and adhesion. Such widespread genomic alterations cause disruption of normal cellular signaling and finally lead 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 gene promoters differ according to the individual targeted gene. In HCC, incidence of genetic alterations is relatively rare and is limited to a subset of few cancer-specific genes, such as the tumor suppressor p53, RB genes and oncogenes such as the CTNNB1. In contrast, epigenetic changes that involve aberrant methylation of genes and other post-transcriptional histone modifications occur far more frequently...