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p16基因改变与表达和胰腺癌关系的研究

[Study on the relationship of alteration and expression of p16 gene to pancreatic carcinoma].

作者信息

Zhou J, Yang D, Zhang L, Wang J, Yao Q, Su Z, Fan Y

机构信息

Department of Bile-pancreatic Surgery, the Genetic Centre, the Affiliated Hospital of Nanjing Railway Medical College, Nanjing, Jiangsu, 210009 P.R. China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2000 Dec;17(6):399-403.

Abstract

OBJECTIVE

To directly investigate the effect of genetic alteration(homozygous deletion and point mutation) and expression of p16 gene on pancreatic carcinomas.

METHODS

Thirty-five cases were analyzed for genetic alteration and expression of p16 gene by polymerase chain reaction(PCR), single strand conformation polymorphism(SSCP), DNA sequencing and immunohistochemical method.

RESULTS

The analysis of pancreatic carcinoma for p16 gene revealed alteration in 19 of 35 cases, among which 12 pancreatic carcinomas had 522 bp homozygous deletion at least and 7 cases had two point mutations at the same site. One of them is 126th codon GTC --> AAT (Val126Asn); the other is 127th codon GCA --> GCG (A127A). The 3D (three-dimensional) structure of P16 protein determined by computer techniques according to PDB indicated that Val126Asn influenced the space structure of P16 protein and affected the function of P16 protein. Twelve cases revealed no P16 protein and 9 cases showed low level expression of P16 protein.

CONCLUSION

The alteration of p16 gene and abnormal expression of P16 protein are significantly correlated with the biological behavior and clinical staging of pancreatic carcinoma and may hence be helpful to prognostication

摘要

目的

直接研究基因改变(纯合缺失和点突变)及p16基因表达对胰腺癌的影响。

方法

采用聚合酶链反应(PCR)、单链构象多态性(SSCP)、DNA测序及免疫组化方法对35例胰腺癌患者进行p16基因的基因改变及表达分析。

结果

35例胰腺癌患者中,p16基因分析显示19例有改变,其中12例胰腺癌至少有522 bp的纯合缺失,7例在同一位置有两个点突变。其中一个是第126密码子GTC→AAT(Val126Asn);另一个是第127密码子GCA→GCG(A127A)。根据PDB通过计算机技术确定的P16蛋白三维结构表明,Val126Asn影响了P16蛋白的空间结构并影响其功能。12例未检测到P16蛋白,9例P16蛋白呈低水平表达。

结论

p16基因改变及P16蛋白异常表达与胰腺癌的生物学行为及临床分期显著相关,可能有助于预后判断。

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