CDKN2／p16基因5‘—CpG岛SmaⅠ位点甲基化与肺癌的关系

目的 研究ＣＤＫＮ２／ｐ１６基因５’端调控序列ＣｐＧ岛甲基化的状态与肺癌发生发展的关系。方法 采用对甲基化敏感的核酸内切酶ＳｍａⅠ，酶切基因组ＤＮＡ的方法，对８９例肺癌标本和１０例正常肺组织的ＣＤＫＮ２／ｐ１６，基因进行Ｓｏｕｔｈｅｒｎ杂交分析。结果 ８９例肺癌中，ＣＤＮＫ２／ｐ１６基因甲基化１５例，甲基化频率为１６．９％。４２例ｐ１６蛋白阴性的肺癌患中，有１２例发生甲基化，甲基化频率为２８．６％；另有４７例ｐ１６蛋白阳性患中仅有３例发生甲基化。１０例正常肺组织中均未发现ＣＤＮＫ２／ｐ１６基因有甲基化现象。结论 ＣＤＮＫ２／ｐ１６基因５’端ＣｐＧ岛甲基化是该基因失活的重要机制，是肺癌细胞区别于正常细胞的分子事件之一，可能参与肺癌的发生发展过程。

Correlation between methylation on SmaI locus of the CDKN2/p16 gene CpG island and lung cancer

OBJECTIVE: To study the relationship between the status of methylation of the CDKN2/p16 gene 5'-CpG island and lung cancer. METHODS: Genomic DNA was digested with methylation-sensitive enzyme SmaI and Southern blotting was applied to analyze the status of methylation of the CDKN2/p16 in 89 cases of lung cancer and 10 cases of normal lung tissue. RESULTS: Of the 89 cases of lung cancer studied, the CDKN2/p16 gene was shown to be methylated in 15 cases (16.9%). It occurred in 12 of 42 p16 protein negative cases (28.6%), and in 3 of 47 p16 protein positive cases. The CDKN2/p16 gene was not shown to be methylated in 10 cases of normal lung tissue. CONCLUSION: Methylation of the CDKN2/p16 gene 5'-CpG island may be an important mechanism for gene inactivation in lung cancer progression.