摘要
目的 了解肝内胆管癌 (ICC)在发生和发展过程中基因变异特点及其与临床病理学特征的关系。方法 采用微量组织切割法 ,从 2 2份ICC石蜡包埋组织块中提取基因组DNA ,经PCR扩增、琼脂糖凝胶电泳分离和DNA直接测序 ,检测 6种肿瘤抑制基因 (APC、MCC、DCC、OGG1、p5 3和RB1)的杂合性缺失和Ki ras 2癌基因点突变的状况 ,分析其与临床病理学指标的关系。结果 7种肿瘤基因变异的总检出率为 86 .4% (19/2 2 )。根据变异基因类型与临床病理学特征的关系 ,将 19例有基因变异的病例分为两型 :Ⅰ型患者 9例 ,47.4% ,具有APC、MCC、DCC和Ki ras 2基因变异 ,平均年龄 5 7.2岁 ;Ⅱ型患者 10例 ,5 2 .6 % ,具有p5 3、OGG1和RB1基因变异 ,平均年龄 6 9.1岁 (P <0 .0 5 ) ;Ⅰ型患者的术后 3年生存率为 88.9% (8例 ) ,明显高于Ⅱ型患者的 30 0 % (3例 ,P <0 .0 5 )。结论 ICC的发生和发展与多基因变异的长期蓄积和协同作用密切相关 ;Ⅰ型基因变异 (APC、MCC、DCC和Ki ras 2 )主要在ICC的启动和早期演进阶段起作用 ,Ⅱ型基因变异 (p5 3、OGG1和RB1)则在促进ICC的晚期演进过程中发挥作用。
Objective To evaluate the pedigree of genetic alterations during the tumorigenesis of intrahepatic cholangiocarcinoma (ICC) and their correlation with clinicopathological features by analysis of loss of heterozygosity (LOH) in 6 tumor suppressor genes (APC、MCC、DCC、OGG1、p53 and RB1) and point mutations in Ki-ras-2 oncogene. Methods Genomic DNA was isolated from paraffin-embedded slides of 22 surgically resected ICC cases by microdissection-based PCR amplification and agarose gel electrophoresis. Genetic alterations were analyzed by direct DNA sequencing. Results The total frequency of alterations in 7 genes studied was 86.4% (19/22). Based on the pattern of altered genes and their correlation with clinicopathological parameters, the genetic alterations were classified into two groups: Group Ⅰ (9/19, 47.4%) : alterations in APC、MCC、DCC and Ki-ras-2,); Group Ⅱ (10/19, 52.6%): alterations in p53、OGG1 and RB1. The average age of patients in Group Ⅰ (mean age, 57.2 years) was significantly younger than those in Group Ⅱ (mean age, 69.1 years) (P<0.05). Conclusions The occurrence and development of ICC was closely related with the accumulation and cooperation of multiple genetic alterations. The genetic alterations of APC、MCC、DCC and Ki-ras-2 may play crucial roles in the early stage of development of ICC, and the genetic alterations of p53、OGG1 and RB1 may play important roles in accelerating advanced progression of ICC. The detection of the pedigree of genetic alterations in ICC may provide useful information for evaluating the state of tumor progression and clinic prognosis.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2001年第3期183-187,共5页
Chinese Journal of Pathology
基金
上海市卫生系统百名跨世纪优秀学科带头人培养计划资助项目 (98BR0 0 7)
关键词
肝内胆管癌
杂合子丢失
遗传学
预后
基因变异
TSGs
Liver neoplasms
Cholangiocarcinoma
Loss of heterozygosity
Variation (genetics)
Prognosis
