Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia

Objectives To investigate patients with acute lymphoblastic leukemia (ALL) for TEL/AML1 fusion,BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and to determine the relationship and the significance of those findings.Methods Fifty-one American patients (34 men and 17 women) were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL.Chromosome metaphases of each sample were prepared according to standard protocols.Fluorescence in situ hybridization was performed using commercially available DNA probes, including whole chromosome painting probes, locus specific probes, specific chromosome centromere probes and dual color/multiple color translocation fusion probes. The digital image analysis was carried out using Cytovision and Quips FISH programs.Results An overall incidence of chromosomal anomalies, including t (9; 22 ), MLL gene rearrangements, t (12;21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 was found in 33 patients (65%). Thirty-one of them were pediatric patients and two adults. The t(12;21) was the commonest chromosomal anomaly detected in this population; 14 out of the 45pediatric patients (31%) were positive for TEL/AML1 fusion, among which three had an additionalderivative 21[t (12;21) ], four had a deletion of 12p and two had an extra copy of chromosome 21.All 14 patients with positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to standard immunotyping. The percentage of cells with fusion signals ranged from 20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. Three out of the 14 patients positive for the TEL/AML1 gene fusion were originally reported to be culture failures and none of the remaining eleven samples had been found to have chromosome 12 abnormalities by conventional cytogenetic techniques. All pediatric patients with pre-T or T cell lineage and the six adults were negative for TEL/AML1 fusion. One patient had double Philadelphia chromosomes, three had a rearranaement or a deletion of the MLL aene. one had t (4;11)and two had a deletion of the MLL One of the patients with an MLL deletion also had a large ring of chromosome 21, and r (21) was caused by AML1 gene tandemly duplicated at least five times. The second case with the MLL deletion was also unique, the patient had a t (12;21) as well. A total of 20 patients had numerical changes( gain or loss) of chromosomes 4, 10, 17 and 21. Eight patients were found to have trisomies of three or four different chromosomes. Interestingly, seven of these patients did not have TEL/AML1, BCR/ABL or the MLL aene rearranaement, one did have the TEL/AML1 aene fusion. Eleven patients with pro-B cell or B cell type ALL (9 children with ALL, 2 adults with ALL) had numerical changes of chromosome 21 (gain 1 or 2 chromosome 21 ), among them, 10 patients had no structural alteration of chromosome 21, and one was combined by t (12;21 ). Four patients had a monosomy of chromosome 17 and three out of these patients with monosomy 17 also had a fusion signal of TEL/AML1.     

喉鳞癌染色体核型的检测和分析

目的 检测和分析喉鳞癌染色体核形,探讨染色体变异与喉鳞癌基因组变异的关系,及其在肿瘤发生、发展过程中的重要作用.方法 18个来源于喉鳞状细胞癌患者的肿瘤组织进行细胞培养,收集分裂中期细胞,进行染色体"G"带染色,分析核型.并以3例来源于喉鳞癌旁正常上皮组织细胞作为阴性对照.结果 喉鳞癌染色体核型主要表现为大量复杂的、但并非任意性的染色体结构重排和数目改变:染色体丢失的机率显著高于染色体成分、数目的增加;染色体/臂成分的失衡主要表现为3p、4p、8p、18q、5q、13、21和22染色体成分的缺失,及3q、7q、8q、5p、11q13和20染色体成分的增加;大部分的染色体断裂点位于着丝粒区域.结论 染色体数目、结构的不断变异造成癌基因活化、扩增,抑癌基因的抑制和缺失,这种多基因改变的不断积累促进了喉鳞癌的发生及发展.     

滇西地区1512例不明原因不良孕产女性患者染色体分析

目的 探讨原因不明的不良孕产女性患者与异常染色体核型的关系,为进一步寻求临床治疗提供理论依据.方法 回顾性比较分析大理大学第一附属医院自2013年8月至2016年10月接受检查的1512例不良孕产女性患者的检查染色体核型,采用外周血淋巴细胞培养,常规制片及G显带,对每个受检者计数50个核型,分析5个G显带核型.异常者分析核型10个以上.必要时行C和R显带分析.结果 1512例女性患者染色体检查,染色体异常62例,占4%,其中染色体结构异常57例,占91.94%(57/62),成为了异常染色体的主要部分;其分布为性染色体结构异常3例,占4.84%(3/62),常染色体结构异常54例,占87.10%(54/62).数目异常5例,占8.06%(5/62),其中性染色体1例,占1.61%,常染色体4例,占6.45%.结论 原因不明的不良孕产女性患者染色体核型分析能有效地检出异常染色体核型,对于诊断病因、干预以及靶向治疗有着十分重要的作用.     

急性淋巴细胞性白血病的细胞遗传学研究

对40例中国人急性淋巴细胞白血病(急淋)进行了细胞遗传学的研究,发现正常核型为40%,染色体数量异常占42.5%,染色体结构异常为17.5%,特异染色体异常包括有t(9;22)(q34;q11),t(4;11)(q21;q23)和t(8;14)(q24;q32)及环状染色体等.分析了2例急淋患者初发和复发时核型的变化,显示复发时有附加异常。研究认为细胞形态学,免疫表型和细胞遗传学的联合分析(MIC)有助于急淋的诊断和分型。此外,细胞遗传学检查对于急淋白血病的预后具有重要意义。     

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。     

骨髓增生异常综合征的细胞遗传学分析及其预后意义

目的:探讨骨髓增生异常综合征(MDS)的细胞遗传学异常及其演变与MDS的亚型和转归的关系。方法:采用骨髓细胞直接法和(或)短期培养法按常规制备染色体,采用R显带技术进行核型分析。结果:8例MDS检出染色体异常核型,占40%,主要异常有5q-,+8,-7,t/del(3)(q21),-18;MDS-RAEB和RAEBT(63.7%)比MDS-RA(11.1%)异常核型检出率高(P<0.05),且多为复杂异常;核型异常者进展为白血病的危险性明显高于核型正常者。结论:MDS的核型分析对其明确诊断,分型和预后评价有重要的参考价值。     

成人急性淋巴细胞白血病染色体异常及其临床意义

对２７例成人急性淋巴细胞白血病（ＡＬＬ）进行细胞遗传学分析及其临床特征的研究。结果：染色体异常１８例，占６６．７％。检出ＡＬＬ较为常见的特异的染色体异常，如ｔ（９；２２），＋ｍａｒ，ｔ（８；１４）等。本组检出８例ｔ（９；２２），阳性率２９．６％，２例＋ｍａｒ，１例ｔ（８；１４）。提示这些染色体异常可作为ＡＬＬ的一种较为独特的预后因素。     

急性淋巴细胞白血病细胞遗传学改变及其意义

近年来,细胞遗传学在血液病中发挥越来越重要的作用。急性淋巴细胞白血病(ALL)是一类以常染色体结构或数量改变为特征的恶性疾病。ALL最重要的染色体结构改变包括t(9;22)(q34;q11)、t(12;21)(p13;q22)、t(1;19)(q23;p13),形成BCR-ABL、TEL-AML1、E2A-PBX1融合基因。染色体数量异常包括超二倍体、假二倍体、亚二倍体/近单倍体。现就ALL的细胞遗传学改变,细胞遗传学改变与发病机制,细胞遗传学改变与预后的关系以及细胞遗传学指导治疗进行综述。     

荧光原位杂交检测急性髓性白血病21号染色体复杂核型异常

目的对急性髓性白血病（AML）患者可能出现的21号染色体复杂核型异常进行研究。方法AML患者共50例,其中成人37例,儿童13例,采用荧光原位杂交技术（FISH）,运用多种位点特异性DNA探针（染色体全染、特殊位点、双色易位融合探针）进行杂交。结果50例AML中,7例患者出现21号染色体异常（14％）,包括21号染色体数量和结构上的异常。其中4例儿童AML出现21号染色体三倍体,1例合并复杂的核型变化：47～49,XX,der（1）t（1;17）（p36．1;q23）,＋4,＋10,der（11）t（11;17）（q23;q23）,-17,-18,＋20,＋21。3例成人AML出现21号染色体结构的变化,即t（8;21）（q22;q22）。其中1例患者出现复杂的核型变化,即der（21）,t（8;21）（q22;q22）,dup（15q）。结论AML常合并有21号染色体畸变。儿童及成人AML出现21号染色体畸变的方式不同：前者多见21号染色体数量上的变化,而后者多见21号染色体结构上的变化。     

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.     

八探针间期荧光原位杂交技术联合染色体核型分析比较成人与儿童急性淋巴细胞白血病患者的细胞遗传学差异

目的应用八探针间期荧光原位杂交技术(FISH)联合染色体核型分析观察急性淋巴细胞白血病(ALL)成人患者与儿童患者的细胞遗传学差异。方法对125例ALL患者(成人86例、儿童39例)全部行八探针FISH(MYC、P16、E2A、TEL/AML1、BCR/ABL、MLL、IGH、多倍体的DNA探针)检测并染色体核型分析。结果八探针FISH检测结果显示,成人ALL患者与儿童ALL患者的TEL/AML1融合基因、BCR/ABL融合基因与多倍体阳性率之间的差异有统计学意义(P<0.05);染色体核型分析成人ALL患者与儿童ALL患者的(t9;22)易位、多倍体阳性率之间的差异有统计学意义(P<0.05)。结论成人ALL患者与儿童ALL患者融合基因表达各有侧重,不同的细胞遗传学特征与其预后密切相关。FISH多探针诊断系统检测ALL患者常见遗传学异常省时、准确、高效,与染色体核型分析形成很好的互补。     

Cytogenetic studies in women with primary amenorrhea

Cytogenetic investigations were carried out on 117 women with primary amenorrhea who had been referred to our Genetics Laboratory by clinicians throughout Malaysia, after exclusion of other causes of the disorder. Thirty-six cases (31%) showed numerical or structural abnormalities of the sex chromosomes. These can be broadly classified into 4 main types, namely, presence of a Y chromosome (14%), X-chromosome aneuploidies (8%), structural anomalies of the X-chromosome (7%) and lastly, presence of a marker chromosome (2%). Mosaics constituted 17% of the abnormalities observed, always in association with a 45,X cell line. There was no observable correlation between the phenotype of the patients and their respective abnormal karyotypes. The aetiological role of sex chromosomal abnormalities in these amenorrheic women is discussed.     

小儿先天异常的细胞遗传学分析

目的 对临床怀疑染色体病或需排除染色体畸变的患儿进行细胞遗传学染色体检查，以探讨小儿先天异常与染色体异常之间的关系。方法 对小儿先天异常就诊者取外周血，37℃培养，常规制片，G显带，行染色体分析。结果 共检查299例小儿先天异常患者的染色体，其中因智力低下就诊者225例。共发现异常核型129例，占43．14％，其中常染色体数目异常102例，嵌合体4例，常染色体结构异常10例，性染色体数目异常4例，染色体与社会性别不符7例。结论 染色体畸变是小儿先天异常特别是小儿智力低下的主要原因之一。     

染色体核型分析对男性不育诊疗与捐精筛查的意义

目的对不育患者和捐精志愿者进行染色体核型分析,探讨其临床意义。方法对967例不育患者(不育组)和3 184例精液初筛合格的捐精志愿者(捐精组)进行染色体核型分析,比较两组异常核型发生率和异常核型构成情况。结果不育组异常核型发生率显著高于捐精组(14.06%和3.39%,P<0.01)。不育组主要异常核型为非多态性变异,其发生率显著高于捐精组(9.62%和0.25%,P<0.05);捐精组主要异常核型为多态性变异,其发生率与不育组比较差异无统计学意义(3.14%和4.44%,P>0.05)。不育组另发现2例世界首次报道核型,分别为46,XY,t(3;12)(p23;q24)和46,XY,inv(20)(p13;q13.1)。结论染色体非多态性变异是导致男性不育的重要原因之一,对不育患者和捐精志愿者进行染色体核型分析利于优生优育。     

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。     

羊水染色体核型分析降低出生缺陷的研究

目的 探讨羊水染色体异常核型类型、分布及不同产前诊断指征的异常核型检出情况.方法 选取在保定市妇保健院具有产前诊断指征的孕妇1 305例,进行羊膜腔穿刺术及羊水染色体核型分析.结果 1 305例羊水标本共检出异常核型92例,检出率为7.05％,包括数目异常68例(73.91％)和结构异常24例(26.09％);异常核型...     

一例反复自然流产患者的罕见异常核型遗传学研究

运用染色体显带技术对反复自然流产患者进行染色体核型分析，发现染色体结构异常1例，核型为46，xx，t（2；13）（q31；q32），为世界首次报道。本文对染色体异常及反复自然流产产生的原因等进行了讨论。     

Cytogenetic Study on Couples with a History of Reproductive Failure in China

Objective To investigate the incidence of chromosome abnormalities in couples with reproductive failure in China and explore the relationship between chromosome abnormalities and reproductive failure.
Methods A total of 2 158 couples with reproductive failure were enrolled. Lymphocyte culture and harvest were performed according to standard methods. Karyotypes were analyzed by G-banding in all cases and C-banding or R-banding in some cases if necessary.
Results Altogether 137 abnormal karyotypes were found and the chromosomal abnormality rate was 3.17%. Among them 3 were numeral abnormalities, 134 were structural aberrations including 90 cases of reciprocal translocations, 34 cases of Roertsonian translocations, 9 cases of inversions, 1 case of deletion： and 43 kinds of which were identified as the first reported karyotypes in world by the National Teaching Center of Medical Cytogenetics in Hunan, China. Totally 378 chromosome heteromorphisms were also detected and the rate was 8.76%.
Conclusion Structural aberrations were the major abnormal karyotypes in couples with reproductive failure. Reciprocal and Robertsonian translocations occupied the largest proportions in structural aberrations, and a tendency that the rate of chromosome aberration increases with the times of miscarriages was presented. In addition, heteromorphism rate of chromosomes was high in such patients. Chromosome analysis is an important and necessary part of the etiological research in couples with reproductive failure.