Genetic aspects of hepatocellular carcinogenesis
Author(s)
Date
1999Source Title
Seminars in Liver Disease
Print ISSN
0272-8087
Volume
19
Issue
3
Pages
235 - 242
Language
English
Type
ArticleItem Usage Stats
207
views
views
270
downloads
downloads
Abstract
Hepatocellular carcinoma (HCC) is linked etiologically to viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]), chemical carcinogens (i.e., aflatoxins), and other environmental and host factors causing chronic liver injury. Some hepatoblastomas may be linked to inherited gene mutations, but adult hereditary HCC appears to be rare. HCCs display gross genomic alterations, including DNA rearrangements associated with HBV DNA integration, loss of heterozygosity, and, less importantly, chromosomal amplifications and loss of imprinting. Many genes with somatic mutations have now been identified in these tumors. Most frequently involved genes are tumor suppressor genes such as p53, M6P/IGF2R, β-catenin, p16INK4A, and retinoblastoma genes. Most identified mutations are somatic, but germline mutations of p16INK4A, APC, and BRCA2 have also been reported. Oncogenic activation of several cellular genes such as cyclin D and cyclin A have been described in HCC, but the possible implication of candidate viral oncogenes (i.e., X protein of HBV) is still debated. A comprehensive analysis of all the genetic changes described for HCC demonstrates that at least four different growth regulatory pathways are altered in these tumors. However, each pathway appears to be implicated in a limited fraction of these tumors, suggesting that HCCs are genetically heterogenous neoplasms. This genetic heterogeneity correlates with the heterogeneity of etiologic factors implicated in HCC.
Keywords
β- cateninCyclin D
Hepatocellular carcinoma
M6P/IGF2R
P16INK4A
p53
Primary liver cancer
Aflatoxin
Beta catenin
Carcinogen
Cyclin a
Cyclin d
Protein p53
Gene mutation
Hepatitis b virus
Hepatitis c virus