Editorial
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World J Gastrointest Oncol. Jun 15, 2010; 2(6): 259-264
Published online Jun 15, 2010. doi: 10.4251/wjgo.v2.i6.259
From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways
Enzo Ierardi, Rosa Rosania, Mariangela Zotti, Floriana Giorgio, Simonetta Prencipe, Nicola Della Valle, Vincenzo De Francesco, Carmine Panella
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
Author contributions: Ierardi E and Panella C designed the study, revised the manuscript and approved the final version; Rosania R, Zotti M, Prencipe S and Giorgio F collected the data; De Francesco V, Della Valle N and Ierardi E analyzed the data; Rosania R, Zotti M, Prencipe S and Giorgio F drafted the manuscript.
Correspondence to: Enzo Ierardi, MD, Professor, Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Ospedali Riuniti, Viale L. Pinto 71100-Foggia, Italy. enzo.ierardi@fastwebnet.it
Telephone: +39-881-733848 Fax: +39-881-733849
Received: August 27, 2009
Revised: November 24, 2009
Accepted: December 1, 2009
Published online: June 15, 2010
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.

Keywords: Hepatocarcinoma; Chronic liver disorders; Genetic pathways; Molecular pathways; Hepatic growth factors; Augmenter liver regeneration