CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma
Version of Record online: 10 JUN 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 123, Issue 5, pages 998–1004, 1 September 2008
How to Cite
Zhang, C., Guo, X., Jiang, G., Zhang, L., Yang, Y., Shen, F., Wu, M. and Wei, L. (2008), CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. Int. J. Cancer, 123: 998–1004. doi: 10.1002/ijc.23650
- Issue online: 17 JUN 2008
- Version of Record online: 10 JUN 2008
- Manuscript Accepted: 28 MAR 2008
- Manuscript Received: 15 JAN 2008
- National Natural Science Foundation of China. Grant Numbers: 30471994, 30700981
- National High-Tech Research and Development Program of China. Grant Numbers: 2006AA02A304, 2007AA02Z461
- hepatocellular car-cinoma
CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. Telomerase plays an important role in the development of cellular immortality and oncogenesis. To gain insight into the role of epigenetic aberration of telomerase-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in HCC. We examined the promoter methylation status of 9 genes associated with telomerase activity in 120 HCC, 120 cirrhosis tissues and 10 normal liver tissues by methylation-specific PCR. Assay of telomerase activity was by TRAP-ELISA. The frequency of promoter methylation of each gene was P21 63.3%, P15 42.5%, P16 62.5%, P53 14.2%, RB 32.5%, P27 48.3%, WTI 54.2%, E2F-1 70.8% and P300 65.8% of 120 HCC. Methylation status of P21, P15, P16, WTI and E2F-1 was significantly associated with HCC and nontumor tissues (p < 0.05). CIMP+ was detected in 61.7% (74/120) HCC and 15% (18/120) cirrhosis tissues, no CIMP+ was present in normal liver tissues (p < 0.001). A significant difference between CIMP status and metastasis was been found in HCC (p < 0.001). Results showed that 94.6% (70/74) HCC and 55.6% (10/18) cirrhosis patients with CIMP+ show expression of high telomerase activity than 45.5% (10/22) HCC and 6.25% (1/16) cirrhosis patients with CIMP− (p < 0.001). CIMP lead to high levels of expression of telomerase activity through the simultaneous inactivation of multiple genes associated with telomerase activity by concordant methylation. © 2008 Wiley-Liss, Inc.