title: Genetic aspects of hepatocellular carcinogenesis.
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, beta-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.
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Ozturk
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016147:Genes, Tumor Suppressor / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D018095:Germ-Line Mutation; D016174:Hepacivirus / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D009154:Mutation