Insulin-like growth factor 2 gene methylation in peripheral blood mononuclear cells of patients with hepatitis C related cirrhosis or hepatocellular carcinoma.

Abstract

UNLABELLED:

Igf2 gene specific hypomethylation has been demonstrated in hepatocellular carcinoma (HCC) cells and in non-tumoral liver samples from patients with HCV-related cirrhosis who further developed HCC. In patients with colorectal cancers, Igf2 hypomethylation is found in peripheral blood mononuclear cells (PBMC) even prior to the occurrence of cancer.

AIM:

To compare Igf2 methylation in PBMC from healthy donors and patients with HCV-related cirrhosis without or with history of HCC.

PATIENTS AND METHODS:

After DNA extraction from frozen PBMC samples of 52 healthy blood donors and 121 patients with HCV-related cirrhosis either without (n=59) or with past or present HCC (n=62), and sodium bisulfite treatment, unbiased PCR amplification and Denaturing High Performance Liquid Chromatography (DHPLC) analysis were used for methylation analysis at the differentially methylated region 2 of Igf2. Methylation profiles were classified in three groups (unmethylated, U; methylated, M; and intermediate, UM) according to the proportions of M and U alleles, blindly to clinical data. In addition, 677C-T mutation of Methylenetetrahydrofolate Reductase (MTHFR) was investigated by fluorescent probes.

RESULTS:

Prevalences of U, UM and M Igf2 profiles were: 8%, 65% and 27% in blood donors, 0%, 81% and 19% in patients with HCV-related cirrhosis without HCC, 71%, 29% and 0% in patients with HCC (P<0.0001). Igf2 methylation profile was independent from gender, age, body mass index, and presence of 677C-T mutation of MTHFR.

CONCLUSION:

These observations suggest a decrease of Igf2 methylation from cirrhosis to HCC in patients with HCV infection, which may be an additional risk factor for HCC.

• Authors: Philippe Couvert, Alain Carrié, Sophie Tezenas du Montcel, Jenny Vaysse, Angela Sutton, Nathalie Barget, Jean-Claude Trinchet, Michel Beaugrand, Nathalie Ganne, Philippe Giral, Jamel Chelly
• Journal: Clinics and research in hepatology and gastroenterology (Clin Res Hepatol Gastroenterol) Vol. 36 Issue 4 Pg. 345-51 (Aug 2012) ISSN: 2210-741X [Electronic] France
• PMID: 22902352 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• Insulin-Like Growth Factor II

Topics

• Carcinoma, Hepatocellular (complications, genetics)
• DNA Methylation
• Female
• Hepatitis C (complications, genetics)
• Humans
• Insulin-Like Growth Factor II (genetics)
• Leukocytes, Mononuclear
• Liver Cirrhosis (complications, genetics)
• Liver Neoplasms (complications, genetics)
• Male
• Middle Aged
• Retrospective Studies