Methylation profile of the promoter CpG islands of 14 'drug-resistance' genes in hepatocellular carcinoma
| Autor: | Qi Fei, Jing-De Zhu, Hongyu Zhang, Jun Gu, Zu-Bin Shang, Sheng Ding, Peng Wang, Bang-Dong Gong, Jian Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Liver Cancer
Carcinoma Hepatocellular Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator medicine.disease_cause Cell Line Tumor Databases Genetic medicine Humans RNA Messenger Promoter Regions Genetic Gene biology Base Sequence Liver Neoplasms Gastroenterology General Medicine Deoxycytidine kinase Methylation DNA Methylation medicine.disease Molecular biology Cystic fibrosis transmembrane conductance regulator digestive system diseases CpG site Drug Resistance Neoplasm Hepatocellular carcinoma DNA methylation Cancer research biology.protein CpG Islands Carcinogenesis Acyltransferases |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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