肝细胞癌17p13.3位点CpG岛甲基化状态的分析及其意义

ANALYSIS OF METHYLATION STATES OF CpG ISLAND AT LOCUS 17p13.3 AND ITS SIGNIFICANCE IN HEPATOCELLULAR CARCINOMA

为探讨ＤＮＡ甲基化异常在肝细胞癌中的作用，采用Ｓｏｕｔｈｅｒｎ杂交技术对１２例肝细胞癌１７ｐ１３．３位点ＣｐＧ岛甲基化状态进行了检测，发现６例正常肝组织ＣｐＧ岛均未被甲基修饰，而４１．７％（５／１２）的肝细胞癌ＣｐＧ岛被不同程度的重新甲基化；甲基化程度显著升高者多伴１７ｐ１３．３位点的杂合缺失。结果表明：ＣｐＧ岛重新甲基化可能是１７ｐ１３．３位点基因失活的重要机理之一，过度的高甲基化状态与杂合缺失有关。为肝癌的病因学研究提供了资料。

We investigated the methylation of CpG island around the 17p13.3 region in hepatocellular carcinoma (HCC) by Southern blot and found 6 normal liver tissues unmethylated in methlyation sensitive restriction enzyme Not Ⅰ recognized CpG island. However, 41.7%(5/12) HCC cases showed hypermethlation of different extent. 2 HCC cases with more highly hpermethylation accompanied loss of heterozygosity (LOH) at locus 17p13.3. Our results indicate that de novo methylation of CpG island may be an important mechanism for 17p13.3 site gene inactivation and over hypermethylation state may contribute to the LOH of 17p13.3.