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1.
目的:对鼻咽癌中染色体11q13上的4个位点进行微卫星多态性分析,明确这些位点染色体位基因杂合性丢失的情况。方法:采用显微切割的方法获取较纯的肿瘤组织,然后用PCR的方法以PYGM、D11S4946、D11S449和INT-2为引物,对38例鼻咽癌进行微卫生序列分析。结果38例鼻咽癌组织中,至少有一个位点出现杂合性缺失者36例,占94.7%。其中D11S4946杂合性缺失的频率最高,占78.8%(26/33),其余的引物分别为:INT-2占51.5%(17/33),PYGM占45.5%(15/33),D11S449占45.7%(16/35)。结论鼻咽癌染色体11q13区发生高频率杂合性缺失,提示缺失区域可能存在与鼻咽癌发生有关的抑癌基因。 相似文献
2.
鼻咽癌全基因组杂合性缺失分析 总被引:6,自引:2,他引:4
目的:分析鼻咽癌(nasopharyngeal carcinoma,NPS)全基因组染色体杂合性缺失(loss of heterozygosity,LOH),定位NPC发生高频率LOH的区域,为定位NPC相关基因提供分子遗传学依据。方法:用PCR微卫星多态性分析(335个位点)技术检测98例NPC肿瘤基因组DNA等位基因缺失。结果:在22对染色体中,19对染色体在所选取位点中有至少1个位点LOH频率≥30%,3对染色体(15号,20号和22号)无LOH频率大于30%的位点;在335个位点中,4个位点LOH频率≥60%,其中3个在3号染色体,1个在9号染色体;5个位点LOH频率介于50%-59%,其中3个在3号染色体,5号和11号染色体各1个位点;22个位点LOH频率介于40%-49%,52个位点LOH频率介于30%-39%,轼52个位点LOH频率低于30%,提示为背景缺失;LOH频率≥30%的位点主要集中于12个染色体臂,分布于:1p36-34,3p24-26,3p14-21,3q25-27,4q35-31,5q15-21和5q32-33,8p22-23,9p21-23和9q33-34,11p12-14,11q13-23,13q13-14和13q31-32,14q11-13,14q23-24,14q32。本研究新报道在染色体区带1p,5q和19q等发生高频率LOH,LOH精细图谱提示这些区域内可能存在与NPC相关的TSG。结论:NPC肿瘤细胞在多染色体区带发生高频率LOH是常见的分子事件,提示在这些缺失区,可能存在与NPC发生,发展过程中起重要作用的肿瘤抑制基因。 相似文献
3.
胃癌7号染色体长臂的杂合性缺失分析 总被引:2,自引:0,他引:2
目的:检测胃癌患者7号染色体长臂微卫星位点的杂合性缺失(loss of heterozygosity,LOH),以初步确定7号染色体长臂上与胃癌相关基因连锁最密切的微卫星多态位点及LOH的临床意义.方法:在70例原发性胃癌中应用多重PCR技术扩增覆盖整个7号染色体长臂的9个微卫星位点(平均遗传距离为10cm),聚丙烯酰胺凝胶电泳分离PCR产物,用GeneScan、Genotyper软件进行分析.结果:9个微卫星位点的LOH均可发生于原发性胃癌,总的LOH频率为34.3%(24/70),其中D7S486和D7S798位点的LOH频率较高,分别为24.0%(12/50)和19.2%(5/26);总的LOH频率随临床分期而显著增高(P=0.046),D7S486位点的LOH频率在淋巴结转移者显著高于无淋巴结转移者(P=0.015).结论:在7号染色体长臂D7S486和D7S798位点附近,可能存在与胃癌发展相关的抑癌基因. 相似文献
4.
目的 检测原发性肺癌中6号染色体长臂的杂合性缺失。方法 应用PCR-SSLP-银染的方法,选用6号染色体长臂上的5对多态性微卫星标记,对36例原发性肺癌进行了杂合性缺失的研究。结果 36例肺癌中有19例至少在一个位点发生LOH,占52.8%,其中有1例同时在三个位点(D6S310、D6S314、D6S281)发生杂合性缺失。5个位点的LOH频率分别为:16.7%、13.9%、19.4%、5.6%和19.4%。结论 6号染色体长臂的杂合性缺失在原发性肺癌中是常见的染色体改变,并且在丢失的位点附近有一种或几种肿瘤抑制基因与人类原发性肺癌的发生与发展相关联。 相似文献
5.
鼻咽癌染色体16q22-24遗传不稳定性的研究 总被引:5,自引:2,他引:3
目的:研究鼻咽癌染色体16q22-24的遗传稳定性。方法:用染色体16q22-24上的8对微卫星多态性标记分析50例鼻咽癌的杂合性缺失(loss of heterozygosity,LOH)与微卫星不稳定性(microsatellite instability,MSI)。结果:至少一个位点发生LOH的肿瘤占48%(24/50),MSI的发生率为18%(9/50)。但这些变化均散在分布,未见高频共同缺失区和微卫星不稳定区;其变化在早期(Ⅰ/Ⅱ期)和晚期(Ⅲ/Ⅳ期)病人之间有显著性差异(P<0.05)。结论:染色体16q22-24区的遗传不稳定性的变化可能与鼻咽癌的发病有关,该区是否存在鼻咽癌相关基因有待进一步探讨。 相似文献
6.
目的检测乳腺癌组织在染色体17p13区各位点的杂合性缺失。用方法通过Southernblot分析VNTR探针YNZ22的杂合性缺失。用PCR扩增微卫星重复序列后,同位素标记、变性胶分离分析微卫星marker的杂合性缺失。结果11例乳腺癌组织中有3例在染色体17p13.3区有杂合性缺失,占27%。缺失的上限为紧邻端粒的D17S1866位点,缺失至D17S1840位点,缺失的下限尚待确定。位于染色体17p13.1区的TP53位点有1例变化产生新长度的微卫星重复序列,4例存在杂合性缺失,其中2例在17p13.3区也有杂合性缺失。结论乳腺癌组织在染色体17p13.3区有较高的杂合性缺失。预示该区可能存在有关的抑癌基因。17p13.1区的TP53位点也有变化,说明p53基因及产物在乳腺癌的癌变过程中也起着一定的作用 相似文献
7.
8.
肝癌1号染色体等位基因杂合性缺失及临床意义 总被引:2,自引:0,他引:2
研究肝癌1号染色体等痊基因杂合性缺失(Loss of helerozygosity,LOH)及临床意义。方法采用PCR及微卫星多态技术,对65例肝癌1号染色体上28个微卫生标志位点杂合性缺失进行检测。结果:65例肝癌中63例为杂合子,57例至少在1个微卫星标志位点上发生LOH,1号染色体LOH率为91%(57/63),1p76%(48/63),1q88%(52/59);1p36.32-p36.33 相似文献
9.
鼻咽癌染色体3p21-26的等位基因杂合性丢失研究 总被引:7,自引:0,他引:7
目的细胞遗传学研究表明,3号染色体缺失是鼻咽癌常见的染色体异常之一。分子生物学研究表明,染色体3p在鼻咽癌中出现高频率的等位基因杂合性丢失(LOH)。本研究将进一步确定鼻咽癌3p等位基因杂合性丢失的频率及范围。方法应用位于3p2126区域16个微卫星多态性位点,对24例低分化鼻咽癌患者进行了LOH分析。结果24例患者中有16例存在杂合性丢失(66.7%)。丢失频率最高的两个位点是D3S1560(50%,11/21)和D3S1620(50%,9/18)。在具有丢失的16例患者中,8例显示为1个连续的多个相邻位点的杂合性丢失区域,5例患者存在2个或2个以上的杂合性丢失区。病例1,3,4,7,8,10,16,17,18,19和22在D3S1597和D3S1297之间,表现为一个不同大小的杂合性丢失区。结论最小共同丢失区位于D3S1560D3S1620(3p25.326.2)之间,提示该区域有一个尚未克隆的、与晚期鼻咽癌明显相关的抑癌基因。 相似文献
10.
目的探讨等位基因杂合性丢失及微卫星不稳定性在白血病发病过程中的作用及意义。方法采用PCR-非变性聚丙烯酰胺凝胶电泳和硝酸银染色技术,选择位于7q多态微卫星标志序列引物探讨急性白血病等位基因杂合性丢失(LOH)现象。结果在D7S487位点LOH发生率为3.0%(1/33),D7S523发生率为6.1%(2/33),D7S515发生率为15.2(5/33),D7S636发生率为9.1%(3/33),在33例患者中无1例出现微卫星不稳定性(MSI)。20例正常对照标本中无1例出现LOH和MSI。结论7q区域可能存在肿瘤抑制基因(TSG)参与急性白血病的发生发展。 相似文献
11.
Apiwat Mutirangura Wichai Pornthanakasem Virote Sriuranpong Pakpoom Supiyaphun Narin Voravud 《International journal of cancer. Journal international du cancer》1998,78(2):153-156
The main objective of this study was to determine the precise frequency of chromosome 14q loss of heterozygosity in nasopharyngeal carcinomas and to define its minimal deletion regions. Thirty-nine tumors were selected for PCR-based deletion mapping using 19 microsatellite polymorphic markers spanning the long arm of this chromosome. Loss of heterozygosity for at least one marker was observed in 29 (74.4%) tumors, while 24 of these tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated, the first defined by markers D14S278 and D14S288, the second being between D14S51 and the telomere. These data confirmed 2 potential tumor-suppressor-gene loci at 14q12-13 and 14 q32. Interestingly, the third region of loss was located at the T-cell-receptor delta-chain locus. This may reflect another tumor-suppressor-gene locus at 14q11.2, or may be the consequence of a specific genomic rearrangement of this region. In addition, these allelic losses occurred with high frequency in all tumor grades and stages and in all histological sub-types. These findings suggest that the genetic alteration of chromosome 14 is common and crucial during nasopharyngeal-carcinoma development. Int. J. Cancer 78:153–156, 1998.© 1998 Wiley-Liss, Inc. 相似文献
12.
Loss of Heterozygosity Analysis on the Long Arm of Chromosome 7 in Gastric Carcinoma 总被引:1,自引:0,他引:1
Jintian Li Shijuan Mai Bingjian Feng Qisheng Feng Lixi Huang Xingjuan Yu Zhizhong Pan Youqing Zhan Jianchuan Xia 《中国肿瘤临床(英文版)》2004,1(3):153-157
Objective In order to defne the common deleted region related to primary gastric carcinomas in Chinese, the frequency of loss of heterozygosit
(LOH) on human chromosome 7q and its clinicai significance were investigated.
Methods A set of 9 microsatellite markers on 7q with an average genetic distance of l0cM were used to identify LOH by muiti -PCR amplification
of matched tumor and non-tumor DNAs from 70 patients with primary gastric carcinoma. The PCR products were separated by electrophoresis
in poiyacrylamide gels and analysed for LOH by using Genescan and Genotyper software.
Results The total frequency of LOH at any iocus on 7q was 34.3% (24/ 70) in the tumors. Compared fo non -tumor DNA, LOH at D7S486
and D7S798 loci were higher, 24.0% (12/50) and 19.2% (5/26), respectively The total frequency of LOH on 7q was markedly higher
with an increase in the clinical stage (P<0.05). The frequency of LOH at D7S486 in cases with lymph node metastasis was significanty higher than in cases without lymph
node metastasis,P=0.015.
Conclusion The higher incidence of LOH at O7S486 and D7S798 in primary gastric carcinoma compared to normal tissue suggests that the
potential tumor suppressor genes (TSGs) involved in the progression of gastric carcinoma might be nearby these 2 locl.
This work was supported by the National Natureal Science Foundation of China. (No.30070840) 相似文献
13.
Multiple genetic alterations are believed to be involved in the pathogenesis of nasopharyngeal carcinomas (NPC). Loss of heterozygosity (LOH) of chromosomes 3p, 9p and 11q were previously reported in NPC. In order to further define the genetic alterations in NPC, 42 pairs of normal and tumor DNA of NPC were examined for LOH on chromosomes 5p, 5q, 6q, 14q, 15q, 16p, 16q, 17q using 16 polymorphic microsatellite markers. Frequent LOH (33%; 7 out of 21 cases) was observed in chromosome 14q at locus D14s81 (14q31). In order to define the common region of deletion, nine polymorphic microsatellite markers on 14q were examined for LOH in NPC. A common region of deletion was defined in NPC at chromosome 14q24.3-q32.1 flanked by two microsatellite markers D14s76 and D14s45. The common region of deletion (14q24.3-32.1) identified in NPC overlapped with the deleted regions of 14q reported in several human cancers. In 2 cases of NPC, the pattern of LOH revealed the presence of another commonly deleted region defined by loci D14s63 and D14s69 (mapped to 14q11.1-24.1) and located proximal to locus D14s76(14q24.3). This study suggests that multiple tumor suppressor genes present on chromosome 14q are involved in the pathogenesis of NPC. 相似文献
14.
Jintian Li Shijuan Mai Bingjian Feng Qisheng Feng Lixi Huang Xingjuan Yu Zhizhong Pan Youqing Zhan Jianchuan Xia 《中国肿瘤临床(英文版)》1996,1(3):153-157
Objective In order to defne the common deleted region related to primary gastric carcinomas in Chinese, the frequency of loss of heterozygosit
(LOH) on human chromosome 7q and its clinicai significance were investigated.
Methods A set of 9 microsatellite markers on 7q with an average genetic distance of l0cM were used to identify LOH by muiti -PCR amplification
of matched tumor and non-tumor DNAs from 70 patients with primary gastric carcinoma. The PCR products were separated by electrophoresis
in poiyacrylamide gels and analysed for LOH by using Genescan and Genotyper software.
Results The total frequency of LOH at any iocus on 7q was 34.3% (24/ 70) in the tumors. Compared fo non -tumor DNA, LOH at D7S486
and D7S798 loci were higher, 24.0% (12/50) and 19.2% (5/26), respectively The total frequency of LOH on 7q was markedly higher
with an increase in the clinical stage (P<0.05). The frequency of LOH at D7S486 in cases with lymph node metastasis was significanty higher than in cases without lymph
node metastasis,P=0.015.
Conclusion The higher incidence of LOH at O7S486 and D7S798 in primary gastric carcinoma compared to normal tissue suggests that the
potential tumor suppressor genes (TSGs) involved in the progression of gastric carcinoma might be nearby these 2 locl.
This work was supported by the National Natureal Science Foundation of China. (No.30070840) 相似文献
15.
To better characterize abnormalities affecting rat chromosome 1 during mammary carcinogenesis, tumors were induced by nitrosomethylurea in F1 hybrid rats polymorphic at multiple chromosome 1 loci. By means of restriction fragment length polymorphism and microsatellite length polymorphism analyses, we observed loss of heterozygosity or allelic imbalance affecting various loci on the q arm of chromosome 1 in a high percentage of the 49 tumors analyzed. Fifty percent of the tumors showed loss or imbalance affecting the most distal (1q55) INS1 (rat insulin 1 gene) locus. The MT1PA (metallothionein-1 pseudogene a) locus was observed to be affected in 58% of tumors induced in BUF/NCr × ACI/Vsp rats. Most of the losses appeared to have occurred by mitotic recombination. No parental bias was observed on the affected chromosome 1. Tumors were also screened for mutations in codon 12 of the Ha-ras-1 gene, which is located on 1q. We observed an association between the presence of mutation and allelic imbalance. These studies confirm our previous cytogenetic observations of a high level of nonrandom instability affecting rat chromosome 1 during mammary carcinogenesis. The observed loss of heterozygosity may indicate the existence of a putative tumor suppressor gene within the distal half of the 1q arm. These abnormalities, however, could also be related to the early stages of Ha-ras amplification. © 1995 Wiley-Liss Inc. 相似文献
16.
碱基切除修复基因在人鼻咽癌组织和鼻咽非癌组织中的表达及其意义 总被引:1,自引:1,他引:0
背景与目的:碱基切除修复基因对于维护基因组稳定性具有重要的作用,其表达异常与多种肿瘤相关。本实验研究7个重要的碱基切除修复基因(hOGG1,ADPRT,APE1,MBD4,POLB,XRCC1和LIG3)在鼻咽癌及鼻咽非癌组织中的表达及其意义。方法:用RT-PCR方法分析24例鼻咽癌组织和24例鼻咽非癌组织中hOGG1,ADPRT,APE1,MBD4,POLB,XRCC1和LIG3基因的表达。对有表达差异的基因hOGG1和ADPRT进一步用免疫组化的方法在99例鼻咽癌组织和28例鼻咽非癌组织中进行验证。结果:RT-PCR结果表明hOGG1,ADPRT,APE1,MBD4,POLB,XRCC1和LIG3基因在鼻咽癌和鼻咽非癌组织中均表达。其中,hOGG1和ADPRT在鼻咽癌组织中的mRNA水平显著低于鼻咽非癌组织(P<0.001)。免疫组化验证了两基因的蛋白水平在鼻咽癌组织中降低。在鼻咽癌组织和鼻咽非癌组织中,hOGG1基因高表达率分别50.5%和92.8%(P<0.001),而ADPRT基因分别是53.5%和96.4%(P<0.001)。但两基因的表达水平与鼻咽癌的临床分期和预后无关。结论:hOGG1和ADPRT基因的表达降低,可能与鼻咽癌的发生发展密切相关。 相似文献
17.
鼻咽癌新鲜肿瘤组织DNA倍体性与预后的关系 总被引:3,自引:0,他引:3
背景与目的:因肿瘤有生物学异质性,部分肿瘤的预后和TNM分期并不符合;寻找有效的生物学预后指标作为临床分期的补充,可为今后鼻咽癌的个体化治疗提供一个新的依据.本研究探讨初治鼻咽癌患者新鲜肿瘤组织细胞的DNA倍体性与疗效、预后的关系.方法:1999年1月至2000年2月,53例初治鼻咽癌患者进入本研究,其中单纯放疗32例,另21例患者于放疗第4周接受了一个疗程的PF方案化疗.患者治疗前均活检取新鲜肿瘤组织,用流式细胞仪进行DNA倍体检测.结果:53例患者中,二倍体32例(60.4%),异倍体21例(39.6%).不同倍体组患者的年龄、性别、临床分期、N分期、化疗与否的差异无统计学意义(P=0.695、0.657、0.088、0.972和0.335).全组患者中位随访时间73个月(12~84个月).全组5年总生存率65.61%,其中二倍体组为80.92%,异倍体组为42.86%(P=0.002);5年无远处转移生存率二倍体组为84.26%,异倍体组为44.53%(P=0.003);5年无复发生存率二倍体组为92.59%,异倍体组为72.65%(P=0.118).单因素分析结果显示,临床分期是无复发生存率的影响因素,DNA倍体性、临床分期和T分期是总生存率和无远处转移生存率的影响因素.多因素分析结果显示,与总生存率相关的独立预后因素为DNA倍体性(P=0.020)和临床分期(P=0.007),与无转移生存率相关的预后因素亦为DNA倍体性(P=0.017)和临床分期(P=0.011).结论:采用流式细胞术检测新鲜组织细胞的DNA倍体性和临床分期一样可以预测鼻咽癌患者的预后;DNA异倍体患者比二倍体患者更容易出现远处转移而导致治疗失败. 相似文献