共查询到18条相似文献,搜索用时 218 毫秒
1.
目的:探讨错配修复基因hMSH2在散发性大肠癌发生中的作用。方法:应用酚/氯仿法提取44例结直肠癌组织及其相应正常黏膜组织的DNA,用聚合酶链反应和单链构象多态性分析(SSCP)、DNA测序等方法对基因hMSH2外显子5、6、13、15进行突变情况检测,并结合临床病理资料进行分析。结果:44例散发性大肠癌患者中,2例发生hMSH2基因突变,突变率为4.54%。不同临床病理分期的hMSH2基因突变率差异无统计学意义(P〉0.05)。结论:hMSH2基因可能在散发性大肠癌发生过程中起到一定作用,hMSH2基因突变与散发性大肠癌的临床病理分期无关。 相似文献
2.
目的 探讨中国人遗传性非息肉病性结直肠癌(HNPCC)患者hMLH1与hMSH2基因的突变特点.方法 对76个HNPCC家系先证者的DNA样本用PCR法扩增其hMLH1与hMSH2基因的35个外显子,再进行测序以确定突变类型.结果 (1)25个样本发现hMLH1或hMSH2基因突变,总突变率为33%(25/76);(2)检测到的22种突变中:hMLH1基因突变16个,hMSH2基因突变6个;(3)突变类型包括移码突变、无义突变、剪接区突变、错义突变,其中错义突变较多见(hMLH1基因错义突变11个、hMSH2基因5个).结论 中国人HNPCC家系hMLH1和hMSH2突变谱广泛,突变类型多样,hMLH1突变较hMSH2突变多见. 相似文献
3.
遗传性非息肉病性大肠癌诊治研究进展 总被引:1,自引:0,他引:1
遗传性非息肉病性大肠癌(HNPCC)是一种由错配修复基因(MMR)突变造成的常染色体显性遗传病。MMR家族中以hMLH1和hMSH2突变为主。HNPCC在大肠癌体系中占有重要的比例,约占大肠癌的1%~5%。其与散发性大肠癌的一个显著不同之处在于HNPCC患者肠外肿瘤的发病风险亦较高。作者就HNPCC的诊断和治疗研究进展进行了综述。 相似文献
4.
p53和k-ras基因突变在大肠癌发病中的作用 总被引:5,自引:1,他引:4
目的:探讨p53和k-ras基因突变在大肠癌中的临床意义.方法:采用PCR-SSCP方法检测64例大肠癌患者癌组织及癌旁正常粘膜组织的p53和k-ras基因.结果:64例大肠癌患者中发生p53基因突变28例(43.8%),发生k-ras基因突变26例(40.6%),出现p53和kras基因协同突变11例(17.2%).p53和k-ras基因突变与病人性别、肿块部位、大小、浸润深度及Dukes分期无关;k-ras基因突变组年龄略高于非突变组;p53或k-ras基因单一突变组易出现淋巴结转移,但无统计学意义;p53和k-ras基因协同突变组淋巴结转移率(10/11、90.9%)明显高于两者均无突变组(7/21、33.3%,P<0.05).结论:p53和k-ras基因协同突变可能直接或间接促进了大肠癌的进一步发展. 相似文献
5.
散发性大肠癌多基因突变与肠道内环境因素关系的研究 总被引:3,自引:0,他引:3
目的:探讨肠道内环境中因素与散发性大肠癌多基因突变关系。方法:对106例散发性大肠癌患者进行多基因突变和肠道内环境中有关指标(以粪便为标本)的测定,并进行流行病学的病例一病例研究分析。结果:106例散发性大肠癌患者中APC(MCR),K—raS(12/13)及P53(5/6,7,8)突变率分别为31.19%(32/106),37.74%(40/106)及39.62%(42/106)。散发性大肠癌患者p53 249密码子突变占p53总突变的42.86%(18/42);肠道内粪胆汁酸(OR=1.9280,P=0.0052),Mg^2^ (OR=0.287l,P=0.0121)和Ca^2^ (OR=O.0659,P=O.0307)进入多因素logistic模型;吸烟指数和肠道内胆汁酸与p53 249密码子突变相关。结论:散发性大肠癌确实普遍存在有多种基因的突变,肠道内高胆汁酸可能是散发性大肠癌相关基因突变的重要危险因素,肠道内ca^2^ 和Mg^2^ 可能为保护性因素;广东地区散发性大肠癌p53基因突变有一定特点,有必要探索AFB1在广东地区散发性大肠癌发生发展中可能作用。 相似文献
6.
目的:考察遗传性非息肉病性结直肠癌(HNPCC)家系hMLH1/hMSH2生殖系突变的情况.方法:选择13个符合Amsterdam标准的HNPCC家系中的先证者,利用DNA 测序检测hMLH1/hMSH2基因突变情况.对其中不携带hMLH1/hMSH2生殖系突变的HNPCC 家系,利用免疫组化检测hMLH1/hMSH2基因表达、PCR-SSCP检测先证者肿瘤组织的微卫星不稳定性(MSI).结果:13个HNPCC家系的先证者中有3例检测不到hMLH1/hMSH2的生殖系突变.3例无hMLH1/hMSH2突变的先证者中,肿瘤组织的微卫星不稳定检测均为MSI-H,免疫组化检测hMLH1/hMSH2基因表达正常.结论:3个严格符合Amsterdam标准的HNPCC家系中未发现hMLH1/hMSH2基因系突变,提示可能存在其他基因突变导致该3个家系HNPCC肿瘤发生. 相似文献
7.
目的:研究散发性结直肠癌hMLH1(human mutl homolog l,hMLH1) 基因突变的状况.方法:采用PCR-单链构象多态性分析(Polymerase Chain Reaction-Single Strand Conformation Polymorphism, PCR-SSCP),对44例散发性结直肠癌标本hMLH1基因第8、12、14、15和16号外显子进行突变检测.结果:44例标本的hMLH1基因外显子均未发现突变.结论:散发性结直肠癌hMLH1基因突变可能是偶发事件; 散发性大肠癌的发生、发展主要是由于其它基因引起的. 相似文献
8.
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 总被引:10,自引:1,他引:9
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。 相似文献
9.
大肠癌患者粪便p53基因检测及其临床意义 总被引:1,自引:1,他引:0
目的: 研究大肠癌患者p53基因突变及蛋白表达之间关系,并探讨从粪便中检测p53基因突变在大肠癌早期诊断中的临床意义。方法: 采用聚合酶链反应单链构象多态性分析(PCR-SSCP)法,检测大肠癌患者癌组织和粪便标本中p53基因第5~8外显子突变情况;同时运用免疫组化法分析癌组织中p53表达情况。结果: 34例大肠癌患者癌组织标本中,p53基因第5~8外显子突变及蛋白表达阳性率分别为52.9%和55.9%,正常黏膜未见p53表达(P<0.01)。p53表达与基因突变呈正相关关系(P<0.05)。p53表达阳性率与肿瘤组织大小有关,肿瘤≤ 5cm者阳性率高于>5 cm者(P<0.05),但与其它临床病理因素无关。12例癌组织中有p53基因突变的患者其粪便中基因突变阳性率为41.7%,正常人未检测出突变。结论: p53基因突变是参与和影响p53表达和生物学功能的主要因素;大肠癌患者粪便中可检测出p53基因突变,粪便中p53基因检测可成为一种新的肿瘤标志物用于大肠癌的诊断及高危人群的筛检普查。 相似文献
10.
目的 探讨大肠癌错配修复基因hMLH1突变与微卫星不稳 (MSI)的关系。方法 采用二维DNA电泳和DNA测序技术检测hMLH1突变 ;采用PCR为基础的方法检测MSI。结果 76例大肠癌中检出hMLH1基因突变 8例 ,突变率为 10 .5% ,检出MSI 2 0例 ,检出率为 2 6 .3%。右侧大肠癌hMLH1突变和MSI的检出率显著高于左侧大肠癌 (P <0 .0 5 ) ,hMLH1突变与肿瘤大小、分化程度、组织学类型、浸润深度、淋巴结转移和临床病理分期无显著相关。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) 5 6例 3组 ,8例hMLH1基因突变均发生于MSI H组 ,而MSI L和MSS组未见有突变者。结论 hMLH1基因突变与MSI多发生于右侧大肠癌 ,MSI的发生与hMLH1突变有关 相似文献
11.
ThehumanDNAmismatchrepairsystem (MMRS)consistsofaseriesofenzymesthatcancorrectmistakesduringDNAreplication Usingthissystem ,mutationscanbeavoided ,andDNAcanbekeptwholeandstableduringreplication SixgenesofMMRhavebeendefined :hMSH2 ,hMLH1,hMSH6,hMSH3,hPMS1andhPM… 相似文献
12.
EB病毒感染与hMLH1蛋白表达在子宫颈癌发病中的意义 总被引:1,自引:0,他引:1
目的:了解宫颈癌Epstein-Barr病毒(EBV)感染情况及错配修复基因hMLH1表达在宫颈癌发生、发展中的意义。方法:采用免疫组织化学SP法检测临床资料较完整的72例子宫颈鳞癌和31例慢性宫颈炎组织EBV潜伏期膜蛋白(LMP1)与hMLH1蛋白表达,并分析二者的相关关系。结果:在宫颈炎及宫颈癌组EBV(LMP1)的表达率分别为90·3%(28/31)和69·4%(50/72),差异显著(P<0·05);hMLH1的表达率分别为61·3%(19/31)和58·3%(42/72),无显著差异(P>0·05);EBV感染组和非EBV感染组hMLH1的表达率分别为67·5%(54/80)和43·5%(10/23);差异显著(P<0·05);EBV(LMP1)和hMLH1的表达率与宫颈癌的分级、分期及淋巴结转移均无明显相关关系(P>0·05);与是否绝经无明显相关关系(P>0·05)。结论:宫颈炎和宫颈癌EBV感染率均较高,宫颈炎患者宫颈上皮EBV感染可能为致宫颈癌的高危因素,有待于进一步证实。EBV感染时hMLH表达率增高,提示EBV感染引起的宫颈细胞基因突变增多可能为EBV的致癌机制之一。 相似文献
13.
目的探讨人类错配修复基因hMLH1、hMSH2及D53在肺癌组织中的表达及意义。方法运用免疫组织化学sP法对56例肺癌组织中hMLH1、hMSH2及p53的表达进行检测。结果56例肺癌组织中hMLH1的阳性表达率为35%,hMSH2阳性表达率为28.6%,分化程度高者阳性率显著高于分化程度低者(P〈0.01),有淋巴结转移者hMLH1及hMSH2阳性率低于无淋巴结转移者(P〈0.05),不同病理组织学类型之间hMLH1及hMSH2表达无显著差别(P〉0.05);56例肺癌组织中,p53阳性率为51.8%,分化程度低者p53阳性率高于分化程度高者(P〈0.05),有淋巴结转移者p53阳性率高于无淋巴结转移者(P〈0.01),不同病理组织学类型之间p53阳性率无差别(P〉0.05);hMLHI及hMSH2阴性表达者的p53阳性率高于hMLH1及hMSH2阳性表达者(P〈0.05)。结论hMIH1及hMSH2基因的缺陷及p53的表达与肺癌的发生发展过程并与分化程度及有否淋巴结转移有关。 相似文献
14.
Background At least five mismatch repair (MMR) genes, including hMSH2, hMLH1, hPMS, hPMS2, and hMSH6/GTBP, are associated with hereditary nonpolyposis colorectal cancer (HNPCC). More than 90% of families with HNPCC harbor the hMSH2and hMLH1 gene mutations. We have analyzed the clinical features of HNPCC among Chinese patients and report the results of screening for mutations in the hMSH2 and hMLH1 genes.
Methods The data concerning gender, site of colorectal cancer (CRC), age at diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors for 126 patients from 28 independent families with HNPCC were collected. Fifteen of the families met the Amsterdam I criteria, and 13 met the Japanese clinical criteria for diagnosis. Genomic DNA was extracted from the peripheral lymphocytes. Polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding region of the hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced.
Results One hundred and seventy malignant neoplasms were found in the 126 patients, of whom 23 had multiple cancers. Ninety-eight of the patients (77.8%) had colorectal cancers, with an average age at onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germ-line G204X nonsense mutation in the third exon of hMSH2 was found, representing the first mutation in an MMR gene ever found in people of Chinese Mongolian ethnicity.
Conclusions HNPCC is a typical autosomally dominant hereditary disease, characterized by early onset, a predominance of proximal colorectal cancer, and multiple synchronous and metachronous colorectal cancers. DHPLC is a powerful tool for detecting mutations in the hMSH2 and hMLH1 genes, Mutations in the first nine exons of the hMLH1 gene were more common in Chinese patients. 相似文献
Methods The data concerning gender, site of colorectal cancer (CRC), age at diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors for 126 patients from 28 independent families with HNPCC were collected. Fifteen of the families met the Amsterdam I criteria, and 13 met the Japanese clinical criteria for diagnosis. Genomic DNA was extracted from the peripheral lymphocytes. Polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding region of the hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced.
Results One hundred and seventy malignant neoplasms were found in the 126 patients, of whom 23 had multiple cancers. Ninety-eight of the patients (77.8%) had colorectal cancers, with an average age at onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germ-line G204X nonsense mutation in the third exon of hMSH2 was found, representing the first mutation in an MMR gene ever found in people of Chinese Mongolian ethnicity.
Conclusions HNPCC is a typical autosomally dominant hereditary disease, characterized by early onset, a predominance of proximal colorectal cancer, and multiple synchronous and metachronous colorectal cancers. DHPLC is a powerful tool for detecting mutations in the hMSH2 and hMLH1 genes, Mutations in the first nine exons of the hMLH1 gene were more common in Chinese patients. 相似文献
15.
目的:探讨hMLH1和hMSH2蛋白表达在胃癌中的作用及其与HP感染的关系。方法:用免疫组织化学SP法检测83例胃癌中hMLH1和hMSH2蛋白表达情况;用Warthin-Starry银染法观察83例胃癌中HP感染的情况。结果:胃癌中hMLH1、hMSH2蛋白表达缺失率分别为34.94%、21.69%,两者差异无显著性(P>0.05);HP感染阳性胃癌组hMLH1和hMSH2蛋白表达缺失率均显著高于HP感染阴性组(P<0.05);HP感染阳性胃癌MMR蛋白表达在大于50岁、男性、胃窦部、乳头及管状腺癌及高分化组中明显降低(P<0.05)。结论:hMLH1和hMSH2蛋白表达缺失可能在胃癌的发生中发挥同等重要的作用;HP感染可能引起hMLH1和hMSH2蛋白表达的缺失,这可能是HP感染致胃癌的另一分子机制,HP感染阳性胃癌MMR蛋白表达缺失组有特殊的临床病理特征。 相似文献
16.
T K Weber H M Chin M Rodriguez-Bigas B Keitz R Gilligan L O'Malley E Urf N Diba J Pazik N J Petrelli 《JAMA》1999,281(24):2316-2320
CONTEXT: Germline mutations of the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 have been shown to cosegregate with the colorectal cancer phenotype in multiple hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. However, the frequency of these mutations among African American patients with colorectal cancer is unknown. OBJECTIVE: To investigate the frequency of germline alterations of the DNA MMR genes hMLH1 and hMSH2 among African Americans affected by HNPCC and early-age onset colorectal cancer. DESIGN, SETTING, AND PATIENTS: Forty unrelated African American HNPCC and early-age onset colorectal cancer patients (8 women, 3 men) were identified from the cancer registry at a National Cancer Institute-designated referral center, 11 of whom were available for and agreed to study participation from January 1997 to February 1998. The mean age of the subjects was 44 years. An additional 50 age- and sex-matched African Americans without personal or family history of colorectal, endometrial, ovarian, urinary tract, or upper gastrointestinal tract malignancy were also studied as a polymorphism control population. In all subjects, genomic DNA was amplified by polymerase chain reaction for all hMLH1 and hMSH2 exons and screened using single-strand conformation polymorphism (SSCP) analysis. Samples demonstrating significant SSCP shifts underwent automated nucleotide sequencing analysis. MAIN OUTCOME MEASURE: Frequency of hMLH1 and hMSH2 germline alterations in the affected and control subjects. RESULTS: Germline hMLH1 and hMSH2 mutations were detected in 3 (27%) of the African American colorectal cancer probands studied. Each mutation was novel. Two hMLH1 (an A-->T transversion at codon 26 and a GG-->AT substitution across codons 177 and 178) mutations and 1 hMSH2 mutation (a C-->T transition at codon 389) were identified in 3 female study subjects. Six other hMLH1 and hMSH2 alterations were detected but were presumed to be polymorphisms. Neither missense mutation (at codons 26 and 389) was detected in the control population. CONCLUSIONS: The results of our analysis support an association between the 3 mutations reported and predisposition to colorectal cancer. Further studies are needed to define DNA MMR gene-associated colorectal cancer in African Americans, an understudied population at increased risk of fatal colorectal cancer. 相似文献
17.
甲基转移酶1表达质粒对结肠癌细胞错配修复基因甲基化及其表达的影响 总被引:4,自引:1,他引:3
目的 分析DNA甲基转移酶1(Dnmt1)基因的真核表达质粒对人结肠癌细胞错配修复基因甲基化及其转录水平和微卫星不稳定性(MSI)的影响。方法 分别构建含有人的正义Dnmt1(HMT)和反义Dnmt1(THM)的真核表达质粒,将其转染入结肠癌SW1116细胞,以Western印迹实验分析各组细胞Dnmt1蛋白的表达情况。定量PCR检测hMLH1、hMSH2基因的表达。甲基化特异性PCR分析hMLH1、hMSH2启动子区甲基化情况,银染法研究其对微卫星不稳定性的影响。结果 转染正义Dnmt1质粒的细胞hMLH1、hMSH2的启动子甲基化水平升高,基因mRNA表达降低。转染反义Dnmt1质粒可使细胞中hMSH2启动子呈非甲基化状态,基因表达增强。未发现转染正义和反义Dnmt1基因的SW1116细胞存在MSI的变化。结论 重组Dnmt1表达质粒可通过调控人结肠癌细胞中错配修复基因的甲基化影响基因的表达。 相似文献
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错配修复基因启动子甲基化和蛋白表达在葡萄胎的发生及恶变中的作用 总被引:1,自引:0,他引:1
目的探讨错配修复基因hMLH1和hMSH2启动子甲基化和蛋白表达在葡萄胎的发生及恶变中的作用.方法用甲基化敏感性核酸内切酶HpaⅡ酶切-PCR法,分析正常早孕人流绒毛、部分性葡萄胎(PM)、完全性葡萄胎(CM)和侵蚀性葡萄胎(IM)hMLH1和hMSH2启动子甲基化情况;免疫组化检测hMLH1和hMSH2原位蛋白表达.结果在正常早孕绒毛、PM、CM和IM组织中,hMLH1和hMSH2均表达于细胞滋养细胞,合体滋养细胞大多表达阴性,极少数为弱阳性.正常早孕绒毛组织均未发现hMLH1和hMSH2启动子甲基化,而hMLH1和hMSH2表达全部阳性,阳性率为100%,与PM、CM组织相比,启动子甲基化和蛋白表达均存在显著性差异(P<0.05).IM中hMLH1和hMSH2启动子甲基化发生率分别为80.0%(12/15)和73.3%(11/15),与PM、CM相比无显著性差异(P>0.05);IM hMLH1蛋白表达阳性率为54.5%(6/11),与PM、CM相比无显著性差异(P>0.05);而hMSH2蛋白表达阳性率为36.4%(4/11),明显弱于CM,两者比较有显著性差异(P=0.044).CM和IM组织中hMSH2启动子甲基化与其蛋白表达间存在相关性(P值分别=0.001和0.039).结论hMLH1和hMSH2的高表达对正常细胞滋养细胞基因组的稳定性起着重要的作用;hMLH1和hMSH2启动子甲基化的发生和蛋白表达的缺失参与了葡萄胎的发生. 相似文献