Article first published online: 12 OCT 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 6, pages 1704–1712, December 2007
How to Cite
Sobesky, R., Feray, C., Rimlinger, F., Derian, N., Dos Santos, A., Roque-Afonso, A.-M., Samuel, D., Bréchot, C. and Thiers, V. (2007), Distinct hepatitis C virus core and F protein quasispecies in tumoral and nontumoral hepatocytes isolated via microdissection. Hepatology, 46: 1704–1712. doi: 10.1002/hep.21898
GenBank sequence accession numbers: EF652512 to EF652810.
Potential conflict of interest: Nothing to report.
- Issue published online: 28 NOV 2007
- Article first published online: 12 OCT 2007
- Manuscript Accepted: 27 JUN 2007
- Manuscript Received: 21 FEB 2007
- Pasteur Institute of Paris
- European Community VIRGIL Network of Excellence. Grant Number: EU FP2-3 grant LSHM-CT-2004-503359
- Association Francaise pour l'Etude du Foie research fellowship
Hepatitis C virus (HCV) genetic variability may be involved in liver carcinogenesis. We investigated HCV core and corresponding putative F protein genetic variability in hepatocellular carcinoma (HCC) and cirrhotic nodules. Hepatocyte clusters from 7 patients with HCC and HCV1b-related cirrhosis were isolated via microdissection of HCC tissues and 2 nontumoral cirrhotic nodules. The HCV core complementary DNA was cloned and sequenced from each liver compartment and from the serum of 2 patients. Nucleotide diversity and synonymous and nonsynonymous substitutions were analyzed within and between compartments via phylogenetic analysis and Mantel's test. Liver HCV RNA accumulation was lower in HCC. Increased quasispecies diversity and complexity was observed with HCC in 6 of 7 patients. Mantel's test demonstrated marked compartmentalization of quasispecies between HCC and cirrhotic nodules in all 7 patients and also between the 2 nontumoral nodules in 5 of them. Synonymous–nonsynonymous substitution analysis indicated low selection against tumoral core quasispecies in all patients and a more selective pressure against F protein quasispecies in all compartments. In the 2 subjects analyzed, HCC and nontumoral hepatocyte quasispecies were only minor or undetected in serum. Conclusion: In tumoral hepatocytes, low-replicating hepatitis C quasispecies are compartmentalized and more diversified and are subjected to low selective pressure. Our study supports the importance of core genetic variability in hepatocellular carcinogenesis. (HEPATOLOGY 2007.) This is a corrected version of the abstract first published online on 12 October 2007 — the corrected version appears in print.