OPEN IN READ APP
JOURNAL ARTICLE

Promoter hypermethylation of DNA damage response genes in hepatocellular carcinoma

Zhiqin Li, Hongyan Zhang, Jianping Yang, Tielai Hao, Shenglei Li
Cell Biology International 2012 May 1, 36 (5): 427-32
21864295
Aberrant methylation of promoter CpG islands is a major inactivation mechanism of tumour-related genes that play a crucial role in the progression of silencing in human cancers, including HCC (hepatocellular carcinoma). We have examined the promoter methylation status of five important DNA damage response genes in fresh-frozen HCC tissues and cell lines, as well as the possible correlation between methylation patterns and clinical features of the carcinoma. Promoter methylation status of RASSF1A (Ras association domain family 1), CHFR (checkpoint with forkhead and ring finger domains), GSTP1 (glutathione-S-transferase-pi gene), MGMT [O(6)-methylguanine-DNA methyltransferase] and hMLH1 (human mutL homologue 1) were examined by the MSP (methylation-specific PCR) in 70 HCC tissues and five HCC cell lines. The mRNA expression levels of these genes were measured by RT-PCR (reverse transcription-PCR). Methylation frequencies of these genes tested in HCC were 54 (78%) for RASSF1A, 30 (43%) for CHFR, 26 (38%) for GSTP1 and 22 (32%) for MGMT. No hypermethylation was detected for hMLH1 in any case of HCC or HCC cell lines. Moreover, promoter hypermethylation of RASSF1A, CHFR and GSTP1 in both HepG2 and SNU398 cells, and hypermethylation of MGMT in Huh7 cells, were detected. Treatment of three cell lines with 5Aza-dC (5-aza-20-deoxycytidine) restored or increased the expression of these genes, implicating aberrant DNA methylation in transcriptional silencing. Hypermethylation of RASSF1A and patient age were significantly associated. CHFR methylation status showed a statistically significant correlation with HCC progression. Methylation of the RASSF1A, CHFR, GSTP1 and MGMT genes seem therefore to play an important role in the pathogenesis of HCC. These epigenetic changes may have prognostic importance for patients with HCC.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
21864295
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"