Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 1, 2004; 10(23): 3433-3440
Published online Dec 1, 2004. doi: 10.3748/wjg.v10.i23.3433
Methylation profile of the promoter CpG islands of 14 “drug-resistance” genes in hepatocellular carcinoma
Sheng Ding, Bang-Dong Gong, Jian Yu, Jun Gu, Hong-Yu Zhang, Zu-Bin Shang, Qi Fei, Peng Wang, Jing-De Zhu
Sheng Ding, Bang-Dong Gong, Jian Yu, Jun Gu, Hong-Yu Zhang, Zu-Bin Shang, Qi Fei, Peng Wang, Jing-De Zhu, The State-Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200032, China
Author contributions: All authors contributed equally to the work.
Supported by the National High Technology Research and Development Program of China (863 program), No. 2002AA2Z3353 and the Science Foundation of Shanghai Municipal Government, No. 02DJ14056
Correspondence to: Dr. Jing-De Zhu, The State-key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, LN 2200/25, Xie-Tu Road, Shanghai 200032, China. zhujingde@yahoo.com
Telephone: +86-21-64224285 Fax: +86-21-64224285
Received: April 14, 2003
Revised: April 29, 2003
Accepted: May 9, 2003
Published online: December 1, 2004
Abstract

AIM: To establish the DNA methylation patterns of the promoter CpG islands of 14 “drug-resistance” genes in hepatocellular carcinoma (HCC).

METHODS: The methylation specific polymerase chain reaction in conjunction with sequencing verification was used to establish the methylation patterns of the 14 genes in the liver tissues of four healthy liver donors, as well as tumor and the paired non-cancerous tissues of 30 HCC patients.

RESULTS: While 11 genes (ATP-binding cassette, sub-family G (WHITE), member 2(ABCG2), activating transcription factor (ATF2), beta-2-microglobulin (B2M), deoxycytidine kinase (DCK), occludin (OCLN), v-raf-1 murine leukemia viral oncogene homolog (RAF1), ralA binding protein 1 (RALBP1), splicing factor (45 kD) (SPF45), S-phase kinase-associated protein 2 (p45) (SKP2), tumor protein p53 (Li-Fraumeni syndrome) (TP53) and topoisomerase (DNA) II beta (TOP2B)) maintained the unmethylated patterns, three genes displayed to various extents the hypermethylation state in tumor tissues in comparison with the normal counterparts. The catalase (CAT) was hypermethylated in tumor and the neighboring non-cancerous tissue of one case (3.3%). Both glutathione S-transferase pi (GSTpi) (80%, 24/30 in tumor and 56.7%, 17/30 in the paired non-cancerous tissues) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) (CFTR) (77%, 23/30 in tumor and 50%, 15/30 in the paired non-cancerous tissues) genes were prevalently hypermethylated in HCC as well as their neighboring non-cancerous tissues. No significant difference in the hypermethylation occurrence was observed between the HCC and its neighboring non-cancerous tissues.

CONCLUSION: Hypermethylation of promoter CpG islands of both CFTR and GSTpi genes occurs prevalently in HCC, which may correlate with the low expression of these two genes at the mRNA level and has the profound etiological and clinical implications. It is likely to be specific to the early phase of HCC carcinogenesis.

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