Review of genetic and epigenetic alterations in hepatocarcinogenesis

Herath, NI, Leggett, BA and Macdonald, GA (2006) Review of genetic and epigenetic alterations in hepatocarcinogenesis. Journal of Gastroenterology And Hepatology, 21 1: 15-21. doi:10.1111/j.1440-1746.2005.04043.x

Author Herath, NI
Leggett, BA
Macdonald, GA
Title Review of genetic and epigenetic alterations in hepatocarcinogenesis
Journal name Journal of Gastroenterology And Hepatology   Check publisher's open access policy
ISSN 0815-9319
Publication date 2006-01-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/j.1440-1746.2005.04043.x
Volume 21
Issue 1
Start page 15
End page 21
Total pages 7
Language eng
Abstract Hepatocellular carcinoma (HCC) is associated with multiple risk factors and is believed to arise from pre-neoplastic lesions, usually in the background of cirrhosis. However, the genetic and epigenetic events of hepatocarcinogenesis are relatively poorly understood. HCC display gross genomic alterations, including chromosomal instability (CIN), CpG island methylation, DNA rearrangements associated with hepatitis B virus (HBV) DNA integration, DNA hypomethylation and, to a lesser degree, microsatellite instability. Various studies have reported CIN at chromosomal regions, 1p, 4q, 5q, 6q, 8p, 10q, 11p, 16p, 16q, 17p and 22q. Frequent promoter hypermethylation and subsequent loss of protein expression has also been demonstrated in HCC at tumor suppressor gene (TSG), p16, p14, p15, SOCS1, RIZ1, E-cadherin and 14-3-3 sigma. An interesting observation emerging from these studies is the presence of a methylator phenotype in hepatocarcinogenesis, although it does not seem advantageous to have high levels of microsatellite instability. Methylation also appears to be an early event, suggesting that this may precede cirrhosis. However, these genes have been studied in isolation and global studies of methylator phenotype are required to assess the significance of epigenetic silencing in hepatocarcinogenesis. Based on previous data there are obvious fundamental differences in the mechanisms of hepatic carcinogenesis, with at least two distinct mechanisms of malignant transformation in the liver, related to CIN and CpG island methylation. The reason for these differences and the relative importance of these mechanisms are not clear but likely relate to the etiopathogenesis of HCC. Defining these broad mechanisms is a necessary prelude to determine the timing of events in malignant transformation of the liver and to investigate the role of known risk factors for HCC.
Keyword Gastroenterology & Hepatology
Chromosomal Instability
Cpg Island Methylation
Hepatocellular Carcinoma
Microsatellite Instability
Human Hepatocellular-carcinoma
Nonpolyposis Colorectal-cancer
Tumor-suppressor Gene
Factor-ii Receptor
Microsatellite Instability
Dna Methylation
Cpg Methylation
Hmlh1 Promoter
Allelic Losses
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 101 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Aug 2007, 01:59:18 EST