title: From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways.
abstract: Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase re-expression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are non-specific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.
authors.affiliation: Enzo Ierardi, Rosa Rosania, Mariangela Zotti, Floriana Giorgio, Simonetta Prencipe, Nicola Della Valle, Vincenzo De Francesco, Carmine Panella, Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Ospedali Riuniti, Viale L. Pinto 71100-Foggia, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ierardi
authors.forename: Rosa
authors.initials: R
authors.lastname: Rosania
authors.forename: Mariangela
authors.initials: M
authors.lastname: Zotti
authors.forename: Floriana
authors.initials: F
authors.lastname: Giorgio
authors.forename: Simonetta
authors.initials: S
authors.lastname: Prencipe
authors.forename: Nicola Della
authors.initials: ND
authors.lastname: Valle
authors.forename: Vincenzo De
authors.initials: VD
authors.lastname: Francesco
authors.forename: Carmine
authors.initials: C
authors.lastname: Panella