乳腺癌组织中p16基因变异及CpG岛甲基化状态的研究

目的探讨p16基因在乳腺癌中的纯合缺失、突变和甲基化的改变及与乳腺癌发生、发展的关系.方法采用PCR缺失分析、PCR-SSCP及甲基化敏感内切酶-PCR分析方法检测p16基因在39例乳腺癌组织变化状况,并结合临床病理资料进行分析.结果39例乳腺癌组织有6例出现p16基因纯合缺失,3例发生p16基因突变,p16基因变异频率为15.4%,5'CpG岛11例发生甲基化,甲基化率为28.2%.10例良性乳腺病组织中未发现p16基因改变和甲基化.p16基因变异频率、甲基化状态与临床分期和淋巴结转移密切相关.结论p16基因变异、甲基化是乳腺癌中常见的分子改变,它们在乳腺癌的发生、发展过程中扮演着重要的角色.

p16 gene variation and its methylation at 5' CpG island in breast cancer

Objective To investigate the homozygous deletion, mutation and 5'CpG methylation of p16 gene in breast cancer and, analyze the relationship between the structural alterations of p16 gene and carcinogenesis as well as its progression. Methods Deletion and mutation of p16 gene in 39 breast cancers and 10 benign breast tissues were detected by PCR-based deletion analysis technique and PCR-SSCP and, 5'CpG island methylation were detected by PCR-methylation assay with restriction endonuclease, as well as the relationship between the results of detection and the clinical parameters was also analysed. Results Among 39 breast cancers, homozygous deletion and mutation of p16 gene were found in 6 and 3 cases,respectively. The frequency of p16 gene alteration was 15. 4%, methylation was 28. 2%. p16 gene alteration closely correlated with clinical stage and lymph-node metastasis(P<0105). None of p16 gene alteration was found in 10 benign breast tissues. Conclusion The alteration of p16 gene is a frequent molecular event in breast cancer; it may play an important role in carcinogenesis and progression of breast cancer.