四种软组织肿瘤的分子和细胞遗传学研究

作者用染色体分析和ＤＮＡ印迹实验对２５例软组织肿瘤进行了研究，其中恶性纤维组织细胞瘤（ＭＦＨ）８例、横纹肌肉瘤（ＲＭＳ）１３例、Ｅｗｉｎｇ氏肉瘤（ＥＳ）３例、滑膜肉瘤（ＳＳ）１例。在１７例染色体分析标本中，除１例ＭＦＨ和１例ＲＭＳ为正常核型外，均存在染色体数目和结构异常。在ＲＭＳ、ＥＳ和ＳＳ中还检出恒定的染色体异常，ｔ（２；１３）（ｑ３７；ｑ１４）ｔ（１１；２２）（ｑ２４；ｑ１２）和ｔ（Ｘ；１８）（ｐ１１；ｑ１１）。１４例软组织肿瘤ＤＮＡ分别在ＤＩＳ５７、Ｄ２Ｓ４４、ＭＹＬ１－３、Ｄ２Ｓ３、Ｄ１３Ｓ１、Ｄ１３Ｓ３０、ＥＳＤ和Ｄ１７Ｓ５座位上存在等位片段丢失，基因部分缺失、重排及扩增。其中四种肿瘤共有的基因异常为ＤＩＳ５７，三种肿瘤共有的为Ｄ２Ｓ４４及Ｄ２Ｓ３，两种肿瘤共有的为Ｄ１７Ｓ５、ＥＳＤ和Ｄ１３Ｓ３０。本文就上述结果的意义进行了讨论。     

食管癌不同染色体位点上等位基因杂合缺失的研究

应用聚合酶链反应（ＰＣＲ）技术，配合限制片段长短多态现象（ＲＦＬＰ）分析，对２２例食管癌病人３号染色体短臂３ｐ１４～２４，１７号染色体短臂１７ｐ１３．１杂合缺失（ＬＯＨ）进行了测定。结果显示：３ｐ２４、３ｐ２１、３ｐ１４和１７ｐ１３．１位点ＬＯＨ检出情况分别为８／１１、２／４、１／９和６／６，其中３ｐ２４和１７ｐ１３．１位点的ＬＯＨ较高，提示这一位点ＬＯＨ的测定有可能成为食管癌早期诊断的分子标志。实验发现，在３ｐ２４ＥＡｐＭＤ位点的ＬＯＨ检测中，哈萨克族杂合缺失为５／５，汉族为２／４，维吾尔族为１／２，这是否与种族遗传有关，有必要扩大病例进一步研究。     

用微卫星寻找和定位血液系统肿瘤患者丢失的基因

目的：许多血液系统肿瘤的发生与患者染色体易位和基因丢失有关，基因丢失的部位往往存在抑癌基因。用微卫星确定是否发生基因丢失及基因丢失的位置。方法：用ＰＣＲ扩增不同染色体上常见白血病易位断裂点区域附近的１９个微卫星，变性胶凝胶电泳，以及用１１号染色体上的白血病相关ＭＬＬ基因探针做Ｓｏｕｔｈｅｒｎｂｌｏｔ杂交等方法，检测４９例血液系统肿瘤患者基因的杂合性丢失（ｌｏｓｏｆｈｅｔｅｒｏｚｙｇｏｓｉｔｙ，ＬＯＨ）及丢失部位。结果：发现１８例（１８／４９）血液系统肿瘤患者１～７个微卫星位点上存在ＬＯＨ；以１１号染色体微卫星Ｄ１１Ｓ１３０１的丢失最常见；３例（３／１０）急性髓细胞白血病（ＡＭＬ）患者在Ｄ１１Ｓ１３０１位点有ＬＯＨ，其附近有抑癌基因ＷＴ１和ＲＢＴＮ２。３（３／１３）例ＡＭＬ在Ｄ１１Ｓ１３１４有ＬＯＨ，附近有ＢＣＬ１基因。ＤＮＡ杂交检测发现仅３例ＡＭＬ有ＭＬＬ基因重排，其附近ＬＯＨ不多见。结论：急性白血病患者ＬＯＨ发生率较高，白血病患者染色体１１短臂ｐ１３区是抑癌基因丢失较常见的部位。     

食管癌不同染色体位点上等位基因杂合缺失的研究

应用聚合酶链反应（ＰＣＲ）技术，配合限制片段长短多态现象（ＲＦＬＰ）分析，对２２例食管癌病人３号染色体短臂３ｐ１４￣２４，１７号染色体短臂７ｐ１３．１杂合缺失（ＬＯＨ）进行了测定。结果显示：３ｐ２４、３ｐ２１、３ｐ１４和１７ｐ１３．１位点ＬＯＨ检出情况分别为８／１１、２／４、１／９和６／６，其中３ｐ２４和１７ｐ１３．１位点的ＬＯＨ较高，提示这一位点ＬＯＨ的测定有可能成为食管癌早期诊断的分子标志。实     

原发性肝癌全基因组杂合性缺失的研究

目的 研究肝癌全基因组等位基因杂合性缺失（ＬＯＨ）及其临床意义。方法 采用３８２对微卫星标志,对６５例肝癌２２条常染色体等位基因ＬＯＨ进行检测。结果 全组平均杂合子６８．１％。ＬＯＨ〉３０％的有１ｑ、３ｑ、４ｑ、８ｐ、１３ｑ、１６ｑ和１７ｐ。ＨＢｓＡｇ阳性者Ｄ４Ｓ２９６４ ＬＯＨ（６６％）较ＨＢｓＡｇ阴性者（３０％）高（Ｐ〈０．０５）;Ｄ３Ｓ３６８１和Ｄ１７Ｓ９３８ ＬＯＨ者术后复发率（９１％、８     

世界首报6例人类染色体异常核型

目的：本文报道６例世界首报人类染色体异常核型：①４６，ＸＹ，ｔ（１；３）（１ｐ３６；３ｐ２１）；②４６，Ｘ，ｔ（Ｘ；６）（Ｘｐ２２；６ｑ１３）；③４６，ＸＸ，ｔ（５；１２）（５ｑ３１；１２ｑ１３）；④４６，ＸＸ，ｔ（６；１０）（６ｐ１０ｐ；６ｑ１０ｑ）；⑤４５，ｉ（Ｘｑ）／４６，Ｘ，ｉ（Ｘｑ）／４７，ＸＸ，ｉ（Ｘｑ）；⑥４６，ＸＹ，ｄｅｌ（３），ｔ（３；７）（３ｑ２１；７ｑ３３）。就染色体平衡易位患者的表型效应及平衡易位染色体对染色体复合畸变的影响做了初步探讨。方法：细胞遗传学检查由静脉采取外周血，用１６４０培养液，培养淋巴细胞，常规收获细胞、制片，ＧＴＧ显带。镜下计数分析３０个～５０个分裂像，显微摄影分析５个～１０个分裂像，必要时做高分辨及其它带型。结果：６例患者中染色体平衡易位５例、嵌合型Ｘ等臂染色体１例；多次流产２例、连续２次生育巨大畸形儿１例、原发闭经２例、发育过速１例。结论：染色体平衡易位等畸变是造成临床流产、闭经、发育异常、生产畸形儿等疾患的主要原因之一。     

30例儿童急性粒细胞白血病M2亚型细胞遗传学分析

目的 了解儿童急性粒细胞白血病（ＭＡＬ）Ｍ２亚型遗传学特征。方法 初步分析３０例儿童ＡＭＬ－Ｍ２的染色体核型变化。结果 ３０例儿童ＡＭＬ－Ｍ２染色体核型中伴ｔ（８;２１）（ｑ２２;ｑ２２）组点４６．６７％（１４／３０）,正常核型组占３６．６７％（１１／３０）,其它异常核型组占１．６６％（５／３０）,其中有１例为罕见的伴ｔ（８;２１）（ｑ２２;ｑ２２）的亚四倍体核型。结论 证实了ｔ（８;２１）易位染色体为儿童ＡＭＬ－Ｍ２亚型较为特征性的遗传学变化。     

12例原发性胃癌的细胞遗传学异常

本研究采用一种改良的直接制备实体瘤染色体的方法，对１２例原发性胃癌进行了详细的Ｇ显带分析。其中２例具有简单的染色体改变，核型为４８，ＸＸ．＋８，＋２０和４９，ＸＹ，＋２，＋８，＋９，其它１０列人有复杂的染色体结构和数目异常。常见的结构发迹涉及到７、３、１、５和１２号染色体。ｄｅｌ（７ｑ）在８例中出现，ｄｅｌ（３ｐ）和ｄｅｌ（１ｐ）分别在６例和５例中出现。这些结果为寻找胃癌的相关基因提供了有意义的线     

Cytogenetic Abnormalities in Twelve Primary Gastric Cancers

本研究采用一种改良的直接制备实体瘤染色体的方法，对１２例原发性胃癌进行了详细的Ｇ显带分析。其中２例具有简单的染色体改变，核型为４８，ＸＸ，＋８，＋２０和４９，ＸＹ，＋２，＋８，＋９。其它１０例具有复杂的染色体结构和数目异常。常见的结构改变涉及到７、３、１、５和１２号染色体。ｄｅｌ（７ｑ）在８例中出现，ｄｅｌ（３ｐ）和ｄｅｌ（１ｐ）分别在６例和５例中出现。这些结果为寻找胃癌的相关基因提供了有意义的线索。     

应用bcr5’探针检测慢性粒细胞白血病基因重排

应用ｂｃｒ５’探针检测慢性粒细胞白血病基因重排北京医科大学第一医院血液内科武淑兰北京医科大学第一医院实验中心王丽辉Ｐｈ染色体是慢性粒细胞白血病（ＣＭＬ）多能干细胞的克隆标记，系２２号和９号染色体易位ｔ（９；２２）（ｑ３４；ｑ１１）的结果。２２号染色体...     

Analysis of chromosomes in ascitic fluid cells of ovarian carcinoma

Chromosomes in 1620 metaphases of ascitic fluid cells in 20 cases of ovariancarcinoma were analyzed.The results showed that there were marked structuralaberrations aside from significant increase in chromosomal numerical aberrations(85.2%).In the ascitic fluid cells from 12 patients,15 types of marker chromosomes were found,among which t(6;14)(q21;q24)and t(2;6)(q35;p12)were more frequently noted witha rate of 7.84% and 7.59% respectively,which was significantly higher than that of othermarker chromosomes(P<0.01).The findings suggested that,besides t(6;14)(q21;q24),t(2;6)(q35;p12)may also be a specific marker chromosome of ovarian carcinoma.     

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。     

Chromosomal imbalances revealed in primary rhabdomyo- sarcomas by comparative genomic hybridization

Background Previous cytogenetic studies revealed rhabdomyosarcoma. We profiled chromosomal imbalances aberrations varied among the three subtypes of n the different subtypes and investigated the relationships between clinical parameters and genomic aberrations. Methods Comparative genomic hybridization was used to investigate genomic imbalances in 25 cases of primary rhabdomyosarcomas and two rhabdomyosarcoma cell lines. Specimens were reviewed to determine histological type, pathological grading and clinical staging. Results Changes involving one or more regions of the genome were seen in all rhabdomyosarcomal patients. For rhabdomyosarcoma, DNA sequence gains were most frequently （〉30%） seen in chromosomes 2p, 12q, 6p, 9q, 10q, lp, 2q, 6q, 8q, 15q and 18q; losses from 3p, 11p and 6p. In aggressive alveolar rhabdomyosarcoma, frequent gains were seen on chromosomes 12q, 2p, 6p, 2q, 4q, 10q and 15q; losses from 3p, 6p, lq and 5q. For embryonic rhabdomyosarcoma, frequent gains were on 7p, 9q, 2p, 18q, lp and 8q; losses only from 11p. Frequently gained chromosome arms of translocation associated with rhabdomyosarcoma were 12q, 2, 6, 10q, 4q and 15q; losses from 3p, 6p and 5q. The frequently gained chromosome arms of nontranslocation associated with rhabdomyosarcoma were 2p, 9q and 18q, while 11p and 14q were the frequently lost chromosome arms. Gains on chromosome 12q were significantly correlated with translocation type. Gains on chromosome 9q were significantly correlated with clinical staging. Conclusions Gains on chromosomes 2p, 12q, 6p, 9q, 10q, lp, 2q, 6q, 8q, 15q and 18q and losses on chromosomes 3p, 11p and 6p may be related to rhabdomyosarcomal carcinogenesis. Furthermore, gains on chromosome 12q may be correlated with translocation and gains on chromosome 9q with the early stages of rhabdomyosarcoma.     

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     

Cytogenetic and molecular aberrations of multiple myeloma patients: a single-center study in Singapore

Background Much is known about the cytogenetic lesions that characterize multiple myeloma (MM) patients from the USA,Europe,and East Asia.However,little has been published about the disease among Southeast Asians.The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population.Methods Forty-five newly-diagnosed,morphologically confirmed patients comprising 18 males and 27 females,aged 46-84 years (median 65 years) were investigated by karyotyping and fluorescence in situ hybridization (FISH).FISH employing standard panel probes and 1p36/1q21 and 6q21/15q22 probes was performed on diagnostic bone marrow samples.Results Thirty-four cases (75.6％) had karyotypic abnormalities.Including FISH,a total detection rate of 91.1％ was attained.Numerical and complex structural aberrations were common to both hyperdiploid and non-hyperdiploid patients.Numerical gains of several recurring chromosomes were frequent among hyperdiploid patients while structural rearrangements of several chromosomes including 8q24.1 and 14q32 characterized non-hyperdiploid patients.With FISH,immunoglobulin heavy chain (IGH) gene rearrangements,especially fibroblast growth factor receptor 3 (FGFR3)/IGH and RB1 deletion/monosomy 13 were the most common abnormalities (43.4％).Amplification 1q21 was 10 times more frequent (42.5％) than del(1p36) and del(6q21).Conclusions We have successfully reported the comprehensive cytogenetic profiling of a cohort of newly-diagnosed myeloma patients in our population.This study indicates that the genetic and cytogenetic abnormalities,and their frequencies,in our study group are generally similar to other populations.     

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。     

人肺腺癌细胞系PC84045细胞遗传学研究

本研究运用染色体显带技术对人肺腺癌细胞系PC84045进行了细胞遗传学研究。结果表明,该细胞系是一个亚三倍体,染色体众数为66,染色体数目和结构存在众多异常。多倍体细胞占19/144,C-后期核型占22/144。结构异常包括双着丝粒染色体、染色单体裂隙、染色体裂隙及染色体断片、三射体、粉碎化染色体等。还可见比染色体断片小得多的微小体。本文确定了该细胞系的7个标记染色体,涉及的主要断裂点包括3q11和3p21、1p11和1p13,12p13及7q32,并对这些断裂点在肿瘸发生中的意义进行了讨论。     

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 (&gt;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 (&gt;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.     

100对自然流产夫妇的染色体分析

本文对100对自然流产夫妇进行外周血淋巴细胞培养、染色体检查、G带核型分析,发现6例异常,占受检人数的3％,包括平衡易位5例,占受检人数的2.6％,常染色体长臂部分缺失1例,占受检人数的0.6％。查阅资料,t(6;8)(q25;q22),t(58)(P15;P21)和t(12;13)(q24;q22)未见报道。对t(13;14),t(6;8)和t(5;8)三例进行家系调查,发现t(13;14)染色体在其家系中至少传递了两代,t(5;8)染色体至少传递了三代。