Insulin-like growth factor 2 gene methylation in peripheral blood mononuclear cells of patients with hepatitis C related cirrhosis or hepatocellular carcinoma - 08/09/12
, Philippe Giral a, b, h, Jamel Chelly i, j
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Summary |
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.
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Vol 36 - N° 4
P. 345-351 - août 2012 Retour au numéro
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