中国人遗传性非息肉病性结直肠癌临床及遗传学特征分析  

Clinical and genetic characterization of Chinese hereditary nonpolyposis colorectal cancer families

作　　者：王旭林[1] 袁瑛[1] 张苏展[1] 蔡善荣[1] 黄彦钦[1] 许则丰[1] 郑树[1] 

机构地区：[1]浙江大学医学院附属第二医院肿瘤研究所,杭州310009

出　　处：《中华普通外科杂志》2006年第6期419-422,共4页Chinese Journal of General Surgery

基　　金：国家高技术研究发展计划项目(863项目)(2001AA227111)

摘　　要：目的分析中国人遗传性非息肉病性结直肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)家系的临床及遗传性突变特点。方法收集整理符合中国人HNPCC诊断标准的31个家系资料,应用PCR及变性高效液相色谱分析(denaturing high-performance liquid chromatography,DHPLC)筛查hMLH1和hMSH2基因的突变,对DHPLC图形异常的样本进行测序。结果31个家系中共发生136例次恶性肿瘤(多原发肿瘤14例),其中结直肠癌106例次,占所有肿瘤患者的77．9%,诊断年龄均数为48．6±29．0岁；胃癌14例。肿瘤先证者中共检出分属于17个不同家系的23个碱基变异位点,经DNA序列分析,证实10个家系存在10个不同的碱基突变(10/31,32．9%),其中3个为同义突变未引起蛋白质序列的改变,另外7个为病理性改变,分别为错义突变、无义突变、移码突变。这10个突变中7个位点为首次报道。外显子区检测到5个已知SNP,内含子区检测到8个碱基改变。结论(1)符合中国人HNPCC标准家系约有1/3可检出hMLH1、hMSH2基因遗传性种系突变。(2)中国人HNPCC家系以左半结肠癌和直肠癌多见。Objective To analyze the clinical features of Chinese hereditary nonpolyposis colorectal cancer families and to screen the germline mutations of human mismatch repair gene hMLH1 and hMSH2 in the prabands. Methods Thirty-one independent Chinese families were collected in Zhejiang province. All of them met Chinese HNPCC criteria. PCR and DHPLC were employed to screen the mutations. Sequencing analysis was followed to find out the exact mutation site and character in samples showing abnormal DHPLC profiles. Results One hundred and thirty-six malignant neoplasms were found in 107 patients, with 106 cases being diagnosed as colorectal cancer. Gastric cancer is the most common extracolonic cancer （ 10, 3% ） in these families. Twenty-three different sequence variations in hMLH1 and hMSH2 genes were found in 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutation and 2 frameshift mutations. Conclusions （1） Germline mutations of hMLH1 and hMSH2 genes were identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Missense mutation and silent mutation were often seen. （2） Chinese HNPCC families had some particular clinical features, such as a left-sided predominance, less synchronous or metachronous colorectal cancers, and frequent gastric cancer occurrence.

关 键 词：结直肠肿瘤 遗传性非息肉性 DNA突变分析 色谱法 高效液相 癌基因 

分 类 号：R735.3[医药卫生—肿瘤] R446.9[医药卫生—临床医学]