論文 - 詳細
| RRC ID | 39391 |
|---|---|
| 著者 | Matsuda Y, Ichida T, Matsuzawa J, Sugimura K, Asakura H. |
| タイトル | p16(INK4) is inactivated by extensive CpG methylation in human hepatocellular carcinoma. |
| ジャーナル | Gastroenterology |
| Abstract |
BACKGROUND & AIMS:The molecular status of the p16(INK4) tumor-suppressor gene has not been fully elucidated in hepatocellular carcinoma. The aim of this study was to clarify the mechanism that gives rise to inactivation of p16(INK4) in hepatocellular carcinoma. METHODS:The status of p16(INK4) was evaluated in 60 hepatocellular carcinomas by immunohistochemical staining, differential polymerase chain reaction, single-strand conformational polymorphism, methylation-specific polymerase chain reaction, and methylation-sensitive single nucleotide primer extension. RESULTS:Immunohistochemical staining showed that 29 of the 60 tumors exhibited complete loss of p16(INK4) expression. High levels of DNA methylation were detected in 24 of 29 cases of hepatocellular carcinoma with negative p16(INK4) expression, with methylation of 60%-85% of the CpG islands. In contrast, the level of methylation was <25% in tumors with faint p16(INK4) staining, and no methylation was detected in tumors with positive immunostaining. Intragenic alteration of p16(INK4) was detected in 4 cases. CONCLUSIONS:A strong correlation was found between the extent of methylation and the degree of expression of p16(INK4) in tumor tissues, indicating that epigenetic change due to extensive CpG methylation is the main cause of inactivation of p16(INK4) in hepatocellular carcinoma. |
| 巻・号 | 116(2) |
| ページ | 394-400 |
| 公開日 | 1999-2-1 |
| DOI | 10.1016/s0016-5085(99)70137-x |
| PII | S0016508599001602 |
| PMID | 9922321 |
| MeSH | Adult Aged Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* CpG Islands* Cyclin-Dependent Kinase Inhibitor p16 / genetics Cyclin-Dependent Kinase Inhibitor p16 / metabolism* DNA Primers DNA, Neoplasm / analysis Female Gene Expression Regulation, Neoplastic Genes, p16* Humans Immunohistochemistry Liver Neoplasms / genetics Liver Neoplasms / metabolism* Male Methylation Middle Aged Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational |
| IF | 17.373 |
| 引用数 | 175 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |