乳腺癌p16基因的纯合缺失、高甲基化、突变及其表达  

A study on homozygous deletion, hypermethylation, mutation and expression of p16 gene in human breast cancer

作　　者：郭山春[1,2,3] 廖松林[1,2,3] 孟振行[1,2,3] 柳剑英[1,2,3] 黄玫[1,2,3] 王丹[1,2,3] 丁华野[1,2,3] 

机构地区：[1]北京医科大学病理学系 [2]北京济慈乳腺医院病理科 [3]北京军区总医院

出　　处：《中华病理学杂志》1999年第2期105-108,共4页Chinese Journal of Pathology

摘　　要：目的研究ｐ１６基因在乳腺癌中的纯合缺失、高甲基化和突变等结构变化及其与表达之间的关系。方法应用聚合酶链反应（ＰＣＲ）和ＰＣＲ甲基化银染分析技术（ＰＣＲＭＡＳＳ）对６０例乳腺癌和２４例癌旁组织进行了ｐ１６基因纯合缺失和ｐ１６基因第１外显子的甲基化检测；用ＰＣＲ单链构象多态性（ＳＳＣＰ）和ＤＮＡ测序技术进行了ｐ１６基因突变分析；检测了ｐ１６蛋白和ｍＲＮＡ的表达。结果６０例乳腺癌中，检出７例（１１７％）纯合性缺失、１６例（２６７％）高甲基化、４例（６７％）点突变。ｐ１６蛋白、ｍＲＮＡ的阳性率分别为４６７％（２８／６０例）、６５０％（３９／６０例）。结论ｐ１６基因在乳腺癌中有多种形式的结构异常。其结构的变化使ｐ１６表达障碍，其主要机制是ｐ１６基因高甲基化，而ｐ１６基因纯合缺失和突变仅为次要原因，ｐ１６基因表达异常参与了乳腺癌的进展及转移。Objective To investigate the homozygous deletion (HZD), hypermethylation and mutation of p16 gene in human breast cancer and the relationshsip between the structural alterations of p16 gene and its expression. Methods PCR and PCR methylation assay with silver staining (PCR MASS) were used to detect HZD and hypermethylation of p16 gene exon 1 in 60 fresh breast cancers and 24 normal breast tissues adjacent to cancer (as control tissues). PCR SSCP and DNA sequencing were used for the analysis of p16 gene mutation. Moreover, p16 gene and mRNA were also detected in the 60 cases. Results Of the 60 breast cancers, HZD was found in 7 cases, hypermethylation and mutation were found in 16 and 4 cases respectively, and the difference was statistically significant. The positive rates of p16 protein and mRNA in breast cancer were 28/60 and 39/60 respectively. Conclusion The results demonstrate that several kinds of p16 gene structural changes exist in breast cancer. The structural changes of p16 gene cause abnormal p16 expression, the main mechanisms are hypermethylation, while HZD or mutation are the secondary causes. Abnormal expression of p16 gene then becomes involved in the development and metastasis of breast cancer.

关 键 词：乳腺肿瘤 DNA突变分析 甲基化 基因缺失 基因.p16 

分 类 号：R737.902[医药卫生—肿瘤]