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| 1 | Clinical features and mismatch repair gene mutation screening in Chinese patients with hereditary nonpolyposis colorectal carcinoma显示文摘AIM: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly- inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young age. It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1. The purpose of this study was to analyze the clinical features of Chinese HNPCC patients and to screen hMSH2 and hMLH1 gene mutations.METHODS: Twenty-eight independent Chinese families were collected, of which 15 met Amsterdam criteria I and 13 met the Japanese clinical diagnosis criteria. The data were recorded including sex, site of colorectal cancer (CRC),age of diagnosis, history of synchronous and/or metachronous CRC, instance of extracolonic cancers, and histopathology of tumors. Peripheral blood samples were collected from all pedigrees after formal written consents were signed. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding regions of hMSH2 and hMLH1 genes. The samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer.RESULTS: One hundred and seventy malignant neoplasms were found in one hundred and twenty-six patients (multiple cancer in twenty-three), including one hundred and twentyseven CRCs, fifteen gastric, seven endometrial, and five esophageal cancers. Seventy-seven point eight percent of the patients had CRCs, sharing the features of early occurrence (average age of onset, 45.9 years) and of the right-sided predominance reported in the literature. In Chinese HNPCC patients, gastric cancer occurred more frequently, accounting for 11.9% of all cancers patients and ranking second in the spectrum of HNPCC predisposing cancers. Synchronous CRCs occurred less frequently, only accounting for 3.1% of the total CRCs. Twenty percent of the colorectal patients had metachronous CRCs within 10 years after operation. Eight hMSH2 or hMLH1 gene sequence variations were found in twelve families, including the first Mongolian kindred with a hMSH2 gene mutation.CONCLUSION: HNPCC is characterized by an early-age onset, proximal predominance of CRC, multiple metachronous CRCs, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous CRCs are the remarkable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening, hMLH1 gene mutations, especially of the first nine exons, have been found more common than hMSH2 gene mutations in Chinese patients. Three of seven mutations have been found to be novel, and the germline G204X nonsense mutation in the third exon of hMSH2 has become the first MMR gene mutation found in Chinese Mongolian people. | Shan-RunLiu BoZhao Zhen-JunWang Yuan-LianWan Yan-TingHuang | 2004 | World Journal of Gastroenterology2004，10，18： | 19 |
| 2 | 遗传性非息肉病性结直肠癌患者的临床特点及hMSH2与hMLH1种系突变的筛查显示文摘目的 分析我国遗传性非息肉性结直肠癌 (HNPCC)患者的临床特点 ,报告hMSH2和hMLH1基因突变筛查结果。方法 共收集了 2 8个家系 ,其中 15个家系符合阿姆斯特丹Ⅰ标准 ,13个家系符合日本临床诊断标准。记录的数据包括患者性别 ,结直肠癌发生的部位 ,诊断年龄 ,是否具有同时和 /或异时结直肠癌及结肠外癌 ,肿瘤的组织病理特点等。通过PCR及变性高效液相色谱分析(DHPLC)筛查hMSH2和hMLH1基因的突变 ,然后对DHPLC图形异常的样本进行测序。结果 12 6例患者共诊断 170例次恶性肿瘤 (2 3例患有多原发癌 )。 98例 (77 8% )的患者患有结直肠癌 ,且发病年龄早 (平均 4 5 9岁 ) ,右侧癌多见。共在 12个家系中发现 8种hMSH2或hMLH1基因序列改变 ,其中hMSH2基因的第 3个外显子的无义突变即G2 0 4X是发现的首例我国蒙古族家系错配修复 (MMR)基因突变。结论 HNPCC患者是恶性肿瘤 (尤其是结直肠癌 )的高发人群。DHPLC是一种非常有效的筛选hMSH2和hMLH1基因突变的方法。在我国hMLH1基因尤其是其前九个外显子的突变较hMSH2基因的突变更常见。 | 刘善润 王振军 赵博 万远廉 黄莚庭 | 2004 | 中华医学杂志2004，84，9： | 13 |
| 3 | Arterial chemotherapy of 5-fluorouracil and mitomycin C in the treatment of liver metastases of colorectal cancer显示文摘AIM: Regional chemotherapy using hepatic arterycatheters is a good method of treating patients withcolorectsl cancer liver metastases. We investigated thesurvival of patients with liver metastases fromcolorectal cancer using 5-fluorouracil (5-FU) andmitomycin C Cthrough implantable hepatic arterialinfusion pert. METHODS: Seventy-five patients with inoperable livermetastases from colorectal cancer were includedbetween March, 1992 and November, 2001. We placedimplantable hepatic arterial catheter (HAC) port bylaparotomy. 5-FU, 1 000 mg/m2/d continuous infusionfor five days every four weeks, was delivered in thehepatic arterial catheter through the port. MitomycinC, 30 mg/m2/d infusion in the first day every cyclethrough the port. Response to the treatment wasevaluated by serial determinations of plasma CEA andimaging techniques consisting of computerizedtomography and sonography of liver.RESULTS: Sixty-eight were performed hepatic arterychemotherapy and fifty-six were followed up amongseventy-five HAC patients. Twenty-six patients(46.4 %)have responded and 4 complete remission wereachieved. Eight patients (14.3 %) had stable livermetastases. Twenty-two patients (39.3 %) wereprogressed with increased tumor size and number.Twenty-nine patients(51.8% ) had a decreased serumCEA level, while 10 patients (17.9 %) were stable and17 patients (30.4 %) had an increased serum CEA level.There were no operative death in this series.Complications, which occurred in 18 patients (32.1%),were as followed: hepatic artery thrombosis in 11,Upper gastric and intestinal bleeding in 3, liver abscessin 1, pocket infection in 1, cholangitis in 1, and hepaticartery pseudo-aneurysm in one patient.CONCLUSION: Combined infusion of 5-FU and mitomycinC by hepatic artery catheter port is an effectivetreatment for liver metastases from colorectal cancer.The high response and lower complication rates provethe adjuvant treatment of colorectal cancer with thistreatment. | Lian-Xin Liu Wei-Hui Zhang Hong-Chi Jiang An-Long Zhu Lin-Feng Wu Da-Xun Piao Department of Surgery,the First Clinical College,Harbin Medical University,Harbin 150001,Heilongjiang Province,China Shu-Yi Qi Department of VIP,the First Clinical College,Harbin Medical University,Harbin 150001,Heilongjiang Province,China | 2002 | World Journal of Gastroenterology2002，8，4： | 7 |
| 4 | 错配修复基因hMLH3在家族性胃癌中的突变显示文摘目的:检测错配修复基因hMLH3在家族性胃癌中的突变情况,以探讨hMLH3在家族性胃癌中的作用. 方法:采用聚合酶链反应(PCR)、变性高效液相色谱分析(DHPLC)和直接测序法,检查有遗传背景的16个胃癌家系(共84名成员)的错配修复基因hMLH3突变情况.胃癌家系选择参考以下标准:(1)至少连续两代;(2)至少2例胃癌患者;(3)至少有1例患者为其他患者的一级亲属;(4)至少有1 例患者50岁前被诊断出胃癌. 结果:所有样品的外显子均成功进行PCR扩增,DHPLC分析和基因测序.共在5个家系中发现5处错义突变(31.3%, 5/16),4处在外显子1,另外1处在外显子12.家系6中hMLH3的突变与胃癌发生呈现出较强的相关性,而另外几个家系中的突变情况与胃癌没有表现出明显的相关性.在散发性胃癌及正常对照中未发现突变的存在. 结论:hMLH3基因在家族性胃癌发生中可能为一低风险基因,他可能通过与其他基因互相叠加、共同起作用. | 赵成海 刘宏旭 卜献民 | 2004 | 世界华人消化杂志2004，12，5： | 5 |
| 5 | 国人HNPCC临床病理及错配修复基因突变特点显示文摘目的检测和分析中国人遗传性非息肉性大肠癌(hereditary non-polyposis colorectal cancer, HNPCC)hMSH2和hMLH1基因突变和临床病理特点,并探索高效的检测方法。方法收集31个国人HNPCC家系,采用PCR及变性高效液相色谱分忻(DHPLC)筛查hMSH2和hMLH1基因的突变,对DHPLC图形异常的样本用377DNA测序仪测序。结果31个国人HNPCC家系132个病人中共发现180例恶性肿瘤,其中胃癌19例(10.6%);同时性癌少见,仅占所有结直肠癌(colorectal cancer,CRC)的3.0%。8个家系携带hMSH2或hMLH1基因序列改变,其中包括第一个带有hMSH2基因突变的蒙古族家系。结论国人中胃痛是发病率仪次于CRC的HNPCC相关肿瘤;DHPLC是一种非常有效的筛选hMSH2和hMLH1基因突变的方法;在中国hMLH1基因尤其是其前9个外显子的突变较hMSH2基因的突变更为常见。 | 赵博 王振军 黄筵廷 | 2006 | 医学新知2006，16，4： | 3 |
| 6 | 错配修复缺陷,微卫星不稳定与胃癌显示文摘人类错配修复系统可以识别并纠正DNA复制过程中出现的错误.错配修复系统缺陷使这些错误往往无法消除,导致恶性肿瘤的发生.患者经常表现出微卫星不稳定性.目前发现与人类恶性肿瘤发病有关的错配修复基因包括hMSH2、hMSH3、hMSH6、hMLH1及hMLH3.这些基因的突变在遗传性非息肉病性结直肠癌中的作用已得到广泛证实.临床上很大一部分胃癌患者表现出微卫星不稳定性,提示错配修复缺陷在胃癌的发病中亦起到重要作用.众多的研究发现错配修复基因的突变在胃癌中并不常见,而由于hMLH1启动子甲基化及失活所引起的错配修复缺陷成为胃癌发病机制中—条重要途径.这些患者常具有微卫星不稳定性及独特的临床特征. | 赵成海 | 2004 | 世界华人消化杂志2004，12，6： | 3 |
| 7 | 大肠癌组织微卫星不稳与hMLH1和hMSH2基因启动子区甲基化状态显示文摘目的:探讨大肠癌组织微卫星DNA不稳与hMLH1和hMSH2基因启动子区甲基化状态的关系.方法:采用PCR为基础的方法检测微卫星DNA不稳;采用甲基化特异性PCR方法检测hMLH1和hMSH2基因启动子区的甲基化状态.结果:正常大肠黏膜未见hMLH1和hMSH2基因启动子区的高甲基化.76例大肠癌中检出hMLH1高甲基化8例,占10.5%,而且均为去甲基化和高甲基化并存,未见有hMSH2高甲基化者.检出MSI20例,检出率为26.3%.将MSI分为高频率MSI(MSI-H,≥2个位点)10例、低频率MSI(MSI-L),仅为1个位点10例和MSI阴性(MSS)56例三组,结果右侧大肠癌hMLH1高甲基化检出率(23.1%)显著高于左侧大肠癌(4.0%,P<0.05).MSI-H组hMLH1高甲基化的检出率(8/10)显著高于MSI-L(2/10)和MSS组(6/56,P<0.01-0.001).结论:hMLH1高甲基化与右侧大肠癌的发生有关,可能参与了MSI病理途径,而hMSH2甲基化状态可能与MSI途径无关. | 房殿春 杨仕明 杨建民 刘海峰 彭贵勇 肖天利 汪荣泉 刘为纹 | 2003 | 世界华人消化杂志2003，11，3： | 2 |
| 8 | 遗传性非息肉病性结直肠癌相关肿瘤累计危险度分析显示文摘目的了解各遗传性非息肉病性结直肠癌(HNPCC)相关肿瘤在中国HNPCC家族中发病的危险度,探讨中国HNPCC患者的诊断和治疗策略。方法收集符合Amsterdam标准的HNPCC家族41个,以寿命表法对213例发生各种肿瘤的HNPCC家族成员做相关肿瘤的累计危险度分析。结果肠外肿瘤中胃癌发生率最高(25例),其次为子宫内膜癌(11例)。各HNPCC常见肿瘤的累计危险度分别为大肠癌89.5%,胃癌24.5%,子宫内膜癌29.6%(女性),肝癌8.2%。结论肠外肿瘤中胃癌、子宫内膜癌及肝癌的累计危险度均较高,忽视胃癌在中国HNPCC诊断中的价值,可能会漏诊部分患者。 | 徐烨 邓伟 蔡三军 莫善兢 孙孟红 蔡国响 廉朋 管祖庆 施达仁 | 2005 | 肿瘤研究与临床2005，17，5： | 0 |
| 9 | 毛细管电泳在检测大肠癌hMLH1基因突变中的应用显示文摘目的:建立应用毛细管电泳(CE)联合激光诱导荧光检测(LIF)技术分析单链构象多态性(SSCP)检测人大肠癌hMLH1基因点突变的方法。方法:以PCR法扩增42例散发性大肠癌病人与20名健康志愿者的外周血基因组DNAhMLH1基因第12外显子,采用CELIF法进行SSCP分析,对异常片段用CE直接测序鉴定;研究不同筛分介质(线性聚丙烯酰胺LPA)浓度、分离温度和分离电压对CE行为的影响。结果:42例散发性大肠癌hMLH1基因第12外显子经CESSCP分析发现4例(9.52%)有突变,CE测序证实为T1151A的杂合子点突变,20名健康志愿者未发现突变。较高浓度的LPA(4%~6%)、较低分离温度(20℃)和较高分离电压(9kV)有助于单链DNA峰分离。结论:调整适宜的LPA浓度、分离温度和分离电压可提高CE分析SSCP的效率。应用CELIF技术SSCP分析检测hMLH1基因点突变过程快速、高效、重复性好,适合临床大样本筛查,有望成为检测基因突变的新方法。 | 冯波 郑民华 石先哲 陆爱国 李健文 王明亮 董峰 许国旺 | 2004 | 外科理论与实践2004，9，3： | 0 |
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