肝内胆管癌多基因变异表型分析

目的：探讨参与肝内胆管癌发生的多基因变异谱系，为了肝内胆管癌的发生机理提供基因水平上的依据。方法：采用显微切割术从石蜡组织切片中提取DNA、聚合酶链式反应（PCR）扩增基础上DNA测序的方法，对22例手术切除的肝内胆管癌标本进行了6种肿瘤抑制基因（APC、MCC、DCC、OGG1、p53和RB1）的杂合性缺失（LOH）和Ki-ras-2癌基因点突变的发生率检测。结果7种肿瘤基因的变异率为APC（68．8％）、DCC（46．2％）、OGG1（41．7%）、p53(37.5%)、Ki-ras-2(27．3％）、RB1（22．2％）和MCC（14．3％）。结论多基因变异的协同作用在肝内胆管癌的多阶段发展发生过程中起着重要作用，其中尤以APC、DCC、OGG1、p53和Ki-ras-2构成了肝内胆管癌相关的基本基因谱系。

Genotyping of multiple genetic alterations of intrahepatic cholangiocarcinoma

Objective To provide genetic evidence for understanding the mechanism of oncogenesis of intrahepatic cholangiocarcinoma (ICC) by detecting the multiple genetic spectrums. Methods Twenty-two cases of paraffin-embedded ICC tissue sections were microdissected and genotyped by PCR-based DNA sequencing to detect the frequencies of loss of heterozygosity (LOH) of tumor suppressor genes APC, MCC, DCC, OGG1, p53, and RB1 and of point mutation of Ki-ras-2 oncogene. Results The genetic alteration rate was 68.8% for APC, 46.2% for DCC, 41.7% for OGG1, 37.5% for p53, 27.3% for Ki-ras-2, 22.2% for RB1, and 14.3% for MCC. Conclusion ICC-related genetic spectrum is basically composed of APC, DCC, OGG1, p53, and Ki-ras-2. Multiple genetic alteration plays an important role in the carcinogenesis of ICC.