典型和非典型遗传性非息肉病性大肠癌的研究  

Clinicopathological features of typical and nontypical hereditary non-polyposis colorectal cancer and their germline mutation of hMLH_1 and hMSH_2

作　　者：崔龙[1] 金黑鹰[1] 孟荣贵[1] 阎于悌[2] 王金穗[2] 刘飞 徐洪莲[1] 喻德洪[1] 

机构地区：[1]第二军医大学附属长海医院肛肠外科,上海200433 [2]甘肃省人民医院肛肠外科 [3]南京市中医医院肛肠科全国中医肛肠中心

出　　处：《中华外科杂志》2003年第2期112-115,共4页Chinese Journal of Surgery

基　　金：国家自然科学基金资助项目 (39970 82 3)

摘　　要：目的　研究中国人遗传性非息肉病性大肠癌 (HNPCC)的临床、病理及其hMLH1和hMSH2 基因种系突变的特点。方法　随访 13个典型HNPCC家系 5 4例患者 ,并与 19个非典型HNPCC家系的 3 8例患者进行比较。对典型和非典型HNPCC各 6个家系的先证者进行了hMLH1和hMSH2 基因的PCR SSCP检测 ,对异常者进行测序确定突变类型。　结果　典型HNPCC盲肠、升结肠肿瘤占3 9 7% ,横结肠肝区癌为 5 0 % ;非典型组直肠癌占 65 8% ,2组差异无显著性意义。异时性多原发癌为 11 5 % ,典型HNPCC患者的 3、5、10年的生存率分别为 64 0 %、45 3 %和 3 1 2 % ,而非典型HNPCC组分别为 5 4 4%、42 3 %和 2 6 8% ,2组差异无显著性意义。 12例先证者中 ,PCR SSCP共检测到MLH111外显子 (c3、c1)、hMLH112外显子 (c8)、hMLH118外显子 (c4)、hMSH2 11外显子 (c13 )、hMSH2 1外显子(c6) ,hMSH2 13外显子 (c11)和hMSH2 15外显子 (c4)的异常条带。除MLH111外显子 (c3 )为内含子多态性外 ,6例 (5 0 % )发现 7个外显子的突变 ,测序证实错义突变 4处、插入突变 7处 ,无义突变 1处。结论　中国人的典型HNPCC是一种发病年龄早、近段结肠多见预后较好的大肠癌 ,而通过比较 ,发现中国非典型HNPCC与典型HNPCC非常相似。Objective To study the clinicopathological features of the Chinese hereditary non polyposis colorectal cancer and its germline mutation of hMLH 1 and hMSH 2. Methods Thirteen typical Chinese hereditary non polyposis colorectal carcinoma (HNPC)C kindreds and 19 nontypical HNPCC families were registered and followed up. The germline mutation of the hMLH 1 and hMSH 2 of 12 index cases of 6 typical and 6 nontypical HNPCC were screened by PCR SSCP. Samples with abnomal mobility were sequenced directly. Results The average age of typical HNPCC was 47,no diffrence existed between sexs. Location of the tumors of typical HNPCC represented 44 7% on the right half colon and non typical HNPCC 65 8% on the rectum. The rate of the metachronos cancer was 11 5%. The 3 , 5 and 10 year survival rate was 64 0%, 45 3% and 31 2% respectively. Among 12 cases, 8 showed abnormal mobility. Except for an intron polymorphinism,six exons abnormalities were found in 5 of 12 proband. Sequencing showed 4 missense,7 insertion and a nonsense mutations. Conclusions Chinese HNPCC is early onset, more common on proximal colon and better prognosis. Mutation of hMSH 2 is dorminant in the Chinese typcal HNPCC,but mutation of hMLH 1 is more conmmon in the nontypical group.

关 键 词：结肠直肠肿瘤 遗传性非息肉性 病理学 基因 错配修复 

分 类 号：R735.34[医药卫生—肿瘤]