多形性黄色星形细胞瘤的比较基因组杂交分析

目的研究多形性黄色星形细胞瘤(PXA)的遗传学异常,以探讨该肿瘤的发病机制.方法收集3例PXA标本,应用比较基因组杂交(CGH)分析方法,研究PXA的染色体失衡.应用免疫组化染色,分析表皮生长因子受体(EGFR)在肿瘤细胞中的表达.结果通过CGH分析,在3例PXA中都发现有遗传学异常.其中1例有多条染色体的失衡:2p14-pter、4p15-pter、7p21-qter、11q24-qter、12和15q14-qter的获得,以及8p11.2-pter、9p11-p23、10p12-pter和13q14-qter的丢失.该患者于术后1年死于肿瘤复发.3例肿瘤患者中的2例检测到7号染色体的获得和8号染色体短臂的丢失.免疫组化染色结果显示,EGFR在3例PXA中均呈阴性表达.结论研究PXA的遗传学改变对了解该疾病的发病机制有重要意义.     

自然流产夫妇染色体异常的三例报告

本文报道在80例2次或2次以上自然流产夫妇的细胞遗传学研究中发现的3例染色体异常,其发生率为3.75％。异常染色体核型分别为:46,XX,del(19)(pter→p12)146,XY,t(15;Y)(15qter→15p11::Yq11→Tqter);46,XX,t(3;14)(14qter→14q24::3p27→3qter;14pter→14q24)。结合复习文献,对自然流产夫妇的染色体异常发生率及其临床意义进行了讨论。     

应用比较基因组杂交技术鉴定标记染色体的来源

目的:确定额外标记染色体来源,对染色体异常患者进行明确的遗传学诊断.方法:应用比较基因组杂交(comparative genomic hybridization, CGH)和荧光原位杂交(fluorescence in situ hybridization, FISH)技术对1例小标记染色体患者进行分子细胞遗传学检测.结果:显示13号染色体近着丝粒q11-q12区有一明显扩增,提示该额外小标记染色体来源于13号染色体pter→q12.结论: CGH结合FISH技术是鉴别标记染色体来源的又一快速便捷的方法.     

人体小细胞肺癌细胞系LTEP—sm的细胞遗传学研究

应用G显带技术对我国第一个小细胞肺癌细胞系(SCLC)LTEP-sm进行细胞遗传学研究,共分析分散及显带良好的55代和99代中期相细胞各30个,并对55代及99代各50个中期相细胞进行染色体计数。结果表明,该细胞系55代细胞染色体众数为51～53条,99代为51～54条,基本是一亚三倍体。恒定出现的标记染色体有6个,其中3号染色体短臂缺失即del3p14-23在30个中期相中高达26(55代)及28(99代)个;另5个标记染色体是t(1;15)(1qter→1p22∷15p12→15qter),del(1)(qter→p31:),del(7)(pter→q31:),t(6;9)(6pter→6q14∷9q21→9qter),del(12)(qter→p12.3:)。99代细胞的染色体众数与55代基本一致,且标记染色体完全相同,表明该细胞系遗传结构稳定。     

染色体微小易位致智力障碍家系的遗传学研究

目的应用细胞-分子遗传学及生物信息学分析染色体易位致智力障碍家系病因。方法选用染色体核型分析、基因芯片技术确定智力障碍(ID)患者及染色体微小易位携带者流产胚胎的遗传学改变,生物信息学分析这些改变与ID的关系。结果染色体易位携带者核型均为14和19号染色体的平衡易位;ID患者核型为14q32.2→qter部份三体及19p13.3→pter部份单体,基因芯片检测确定为14q32.2q32.33(101,198,608-107,284,437)×3,19p13.3(260,911-702,733)×1。生物信息学分析发现BSG、HCN2、FGF22和DYNC1H1等基因为关键基因。结论染色体微小易位导致的遗传物质重排更易生育异常后代,染色体末端拷贝数变异与家系中智力低下患者发病有关。     

中枢神经细胞瘤全基因组的比较基因组杂交分析

目的研究中枢神经细胞瘤全基因组的遗传学异常,探讨该肿瘤的发病机制。方法应用比较基因组杂交技术,研究10例中枢神经细胞瘤的遗传学改变。结果10例中枢神经细胞瘤中,6例发现有染色体的失衡,主要表现为遗传物质在染色体2p(4/10)、10 q(4/10)和18 q(3/10)上的获得。结论染色体2p、10 q和18 q的遗传学改变很可能与中枢神经细胞瘤的发病机制有关。     

中枢神经细胞瘤全基因组的比较基因组杂交分析

目的研究中枢神经细胞瘤全基因组的遗传学异常,探讨该肿瘤的发病机制.方法应用比较基因组杂交技术,研究10例中枢神经细胞瘤的遗传学改变.结果10例中枢神经细胞瘤中,6例发现有染色体的失衡,主要表现为遗传物质在染色体2p(4/10)、10q(4/10)和18q(3/10)上的获得.结论染色体2p、10q和18q的遗传学改变很可能与中枢神经细胞瘤的发病机制有关.     

髓母细胞瘤11号染色体的杂合性丢失分析

目的研究髓母细胞瘤的遗传学异常,以探讨该肿瘤的发病机制.方法应用微卫星灶分析方法,研究髓母细胞瘤11号染色体的杂合性丢失(LOH).结果收集20例髓母细胞瘤,应用20个特异性标记物对11号染色体的杂合性丢失进行了分析.结果显示67%的可分析病例具有等位基因的丢失.染色体短臂(11p)和长臂(11q)上的杂合性丢失率分别为27%和13%.同时,在11 p13-15.1上发现了一个共同丢失位点.结论 11 p13-15.1上很可能存在重要的抑癌基因,该基因的丢失可能与髓母细胞瘤的发生有关.     

髓母细胞瘤11号染色体的杂合性丢失分析

目的研究髓母细胞瘤的遗传学异常,以探讨该肿瘤的发病机制.方法应用微卫星灶分析方法,研究髓母细胞瘤11号染色体的杂合性丢失(LOH).结果收集20例髓母细胞瘤,应用20个特异性标记物对11号染色体的杂合性丢失进行了分析.结果显示67%的可分析病例具有等位基因的丢失.染色体短臂(11p)和长臂(11q)上的杂合性丢失率分别为27%和13%.同时,在11 p13-15.1上发现了一个共同丢失位点.结论 11 p13-15.1上很可能存在重要的抑癌基因,该基因的丢失可能与髓母细胞瘤的发生有关.     

142例先天性智能发育不全患儿的遗传学研究

应用细胞遗传学和皮纹分析方法对142例先天性智能发育不全患儿进行了研究。其中,120例正常核型,22例异常核型。异常核型46,XY,t(1;3;21)(1pter→1q32.1∶∶21p11.2→21qter;3 qter→3p26.2∶∶1 q32.1→1 qter)和45,X/45,X,-22,+der(22)t(Y;22)(22qter→22p11.1∶∶Yq11.1→Yq11.2)两种核型国内尚未见报道。皮纹分析结果表明56.7%的患者有1项以上异常皮纹;染色体异常患者均有2项以上异常皮纹;先天愚型患者有“特定”的皮纹改变。     

慢性粒细胞白血病染色体异常的研究

目的 研究慢性粒细胞性白血病急变过程中基因组的异常,方法 对１５例急变期,３例加速期和２０例慢性期的患者进行了常规细胞遗传学分析,用比较基因组杂交和双色染色体涂抹的方法。结果 在所有被研究的病例中均检测到费城染色体,其中１５例演进病例中有１２例还伴有其它的染色体数量和／或结构的异常,而２０例慢性期中仅５例伴其它异常。染色体数量变化是Ｐｈ染色体双体或三体（５／１４例）和８号染色体三体（５／１４）,另     

100例多发性骨髓瘤患者细胞遗传学分析

目的 总结我国多发性骨髓瘤（MM）患者的细胞遗传学特点及其临床意义。方法 回顾性分析我院100例MM患者的细胞遗传学结果。结果 （1）患者总体的克隆性染色体畸变（CA）检出率为17．2％;纳入亚克隆后CA检出率为37．0％;其中哑二倍体最多见;13号染色体异常（C13A）检出率为6．0％,其荧光原位杂交（FISH）检出率为33．3％;14号染色体易位和／或14q32异常检出率6．0％;（2）单因素分析示克隆性CA、非超二倍体和C13A都使患者的总体生存时间（OS）和疾病进展时间（TTP）显著缩短;多因素分析中仅C13A具有独立预后意义。结论 C13A、非超二倍体、超二倍体、免疫球蛋白重链（IgH）易位等CA在我国MM患者中具有重现性。预后分析湿示C13A是独立预后不良因素。     

Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM

Background:

Lung cancer has become the leading cause of death in many regions. Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes. The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM.

Methods:

We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations. In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR).

Results:

We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19. Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations. CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33 and 17p13.1-13.3. And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG).

Conclusions:

The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis. We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33, and 17p13.1-13.3. Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.     

肝外胆管癌瘤细胞染色体的结构畸变

目的 研究肝外胆管癌瘤细胞染色体结构畸变方式和畸变率，筛选肝外胆管癌标记染色体，定位肝外胆管癌相关基因。方法 用比较基因组杂交（CGH）和光谱核型分析（SKY）技术检测12例肝外胆管癌组织瘤细胞染色体结构畸变方式和畸变率。结果 肝外胆管癌瘤细胞多条染色体存在结构畸变，畸变方式以片段重复和丢失为主，重复集中在1q，3q，8q，15q和17q，丢失主要发生在3p，4q，6q，9p，17p和18q，其中丢失率最高的2个区段分别为3p13-p21和9p21-pter（各41．7％）。结论 肝外胆管癌瘤细胞染色体存在明显结构畸变，为进一步定位肝外胆管癌发生发展相关基因靶位点提供科学依据。     

Analysis of comparative genomic hybridization and loss of heterozygosity in 43 primary gastric carcinomas

Objective To investigate common chromosomal changes and the LOH frequency of microsatellite loci in primary gastric cancer samples in order to locate the deleted regions in which human gastric cancer related genes might exist.Methods Comparative genomic hybridization (CGH) was used to define global chromosomal aberrations in 43 primary gastric tumors. Based on the results of CGH, analysis of loss of heterozygosity (LOH) was performed in chromosome 19 in which the loss was first discovered in the gastric cancers. The PCR-based approach was used to investigate 22 loci, which are spaced at 1.1 -10. 9 cM intervals throughout chromosome 19. The amplified PCR fragments were subjected to electrophoresis in PAGE gel and analyzed with GenescanTM and GenotyperTM.Results CGH analysis revealed gains in chromosome 3p(8/43), 8q(8/43), 20 [20 (9/43), 20p(7/43), 20q(4/43)], 12q(16/43), 13q(12/43) and losses in 19 [19 (15/43)], 7 [17 (8/43),17p (10/43)], 16 (10/43) and lp (11/43). Among the 43 evaluated samples, the most frequent LOH was detected at locus D19S571 (27. 81% ).Conclusions The tumorigenesis of gastric cancer includes several chromosomal changes. The aberration of chromosome 19 was the first common change founded in gastric cancer. The region near the D19S571 miclht harbor potential clenes related to the tumoriQenesis of Qastric cancer.     

原发性肝癌实体瘤的细胞遗传学研究

本文用G显带技术对15例原发性肝癌实体瘤作细胞遗传学研究。结果表明肝癌细胞染色体数以非整倍体为主,尤以亚二倍体和亚三倍体为多。各例均出现结构异常的染色体,对其中出现频率较高的20个标记染色体作了简要描述,并提及国内己发表的人肝癌细胞株染色体情况。结果提示某些染色体的断裂可能与肝癌的发生有一定关联。     

Novel chromosomal alterations detected in primary nasopharyngeal carcinoma by comparative genomic hybridization

Objective　To gain a better understanding of genetic changes in Cantonese nasopharyngeal carcinoma (NPC). Methods　Comparative genomic hybridization (CGH) was performed on 17 primary nasopharyngeal carcinomas. Results　A novel copy number gain an chromosome 4q and loss of chromosome 1p were found at a high frequency (>50%). Conclusions　Current analysis revealed a comprehensive profile of the chromosomal regions showing gain of chromosomes 4q, 12q, and 1q as well as loss of chromosomes 1p, 3p, 11q, 14q, 15q, 13q, Xq, 9q, 10p, 10q, and 16q. Frequently altered loci may encode oncogenes or tumor suppressor genes involved in the development of primary NPC.     

Genome-wide allelotype study of primary glioblastoma multiforme

Objective To investigate the molecular genetic pathogenesis of primary glioblastoma multiforme (GBM) and identify which chromosomes or chromosomal regions of the entire genome may harbor tumor suppressor genes (TSGs) associated with GBM.Methods A high-resolution allelotype study of 21 cases of primary GBM was performed by PCR-based loss of heterozygosity （LOH）analysis. Three hundred and eighty-two fluorescent dye-labeled microsatellite markers covering all 22 autosomes were applied. The mean genetic distance between two flanking markers was about 10 cM.Results LOH was observed on all 39 nonacrocentric autosomal arms examined in this study. The LOH frequencies of 10q, 10p, 9p, 17p and 13q were the highest (>50%). Furthermore, high LOH frequencies were detected in the regions containing known TSGs including PTEN, DMBT1, p16, p15, p53 and RB; the LOH frequencies on 14q, 3q, 22q, 11p, 9q, 19q were also high (>40.5%). Our study observed the following commonly deleted regions: 9p22-23, 10p12.2-14, 10q21.3, 13q12.1-14.1, 13q14.3-31, 17p11.2-12, 17p13, 3q25.2-26.2, 11p12-13, 14q13-31, 14q32.1, 14q11.1-13, 22q13.3, 4q35, 4q31.1-31.2, 6q27 and 6q21-23.3. Conclusions The molecular pathogenesis of GBM is very complicated and associated with a variety of genetic abnormalities on many chromosomal arms. The most closely related chromosomal arms to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q. Besides the well-known TSGs including PTEN, DMBT1, p16, p15, p53 and RB, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions detected in the present study.     

食管鳞癌分化相关基因表达谱及其染色体精确定位

基因表达谱,结合临床病理资料筛选食管癌分化相关基因,并在染色体上精确定位。结果:与食管鳞癌分化直接相关的基因有16条,包括MET,KRT4,EGFR,KRT13,CSK,EGR1,CCND1,EPHA2,CEACAM1,PTPN2,HSPBP1,CD-KN1B,BCL2L2,SDC1,CDH1,CTNNA1;主要集中在染色体1p,2p,5q,7p,7q,11q,12p,12q,14q,15q,16q,17q,18p,19q。结论:食管鳞癌发生和演变涉及多条染色体异常的积累。