应用YAC探针进行荧光原位杂交检测慢性粒细胞白血病BCR基因重排

为检测慢性粒细胞白血病（ＣＭＬ）中ＢＣＲ基因重排，采用酵母人工染色体（ＹＡＣ）ＤＮＡ的Ｉｎ－ｔｅｒ－Ａｌｕ－ＰＣＲ产物为探针进行荧光原位杂交（ＦＩＳＨ）研究了１０例ＣＭＬ，其中包括初诊患者２例，ＣＭＬ急变并接受化疗２例，α干扰素治疗２例，自体骨髓移植术（ＡＢＭＴ）后３例和Ｐｈ染色体阴性ＣＭＬ１例。同时进行细胞遗传学和ＲＴ－ＰＣＲ检测。结果：９例ＣＭＬ的４６％～１００％的可分析核型显示ｔ（９；２２）易位，其中携带ｔ（９；２２）细胞最少者为１例自体骨髓移植术后８个月的患者，其６４％的分裂相存在ｔ（９；２２），３６％为正常核型；１例Ｐｈ（－）ＣＭＬ未见ＢＣＲ基因易位，而ＲＴ－ＰＣＲ（＋），提示ＡＢＬ基因片段插入２２ｑ１１，造成隐匿性Ｐｈ染色体。结果表明：应用ＹＡＣ探针进行原位杂交的定位明确。ＦＩＳＨ检测微小残留病（ＭＲＤ）比常规细胞遗传学方法更敏感，而且可以完成ＰＣＲ方法不易进行的定量分析。     

185例白血病骨髓染色体R显带研究

应用染色体Ｒ显带技术对１８５例急慢性白血病骨髓进行研究，异常核型检出率为８７．６％（１６２／１８５），对于质量差的白血病骨髓染色体，Ｒ显带较Ｇ显带成功率高，尤其是末端带畸变者。ＭＤＳ涉及１、３、５、７、８、２０号等染色体异常，ｔ（８；２１）易见于Ｍ２，（１５；１７）见于Ｍ３，ｔ（９；２２）见于９５％ＣＭＬ和少数Ｍ１ＡＬＬ。ＣＭＬ急变还出现ｉ（１７）。双Ｐｈ、＋３、３ｑ－等异常。遗传学检查有助于提高白血病诊断符合率，同时提示染色体复杂畸变的白血病患者预后较差     

常染色体异常与无精子症的关系（附2例世界首报核型）

应用外周血染色体常规制片方法对睾丸无明显损伤史的２４例无精子症患者进行染色体分析发现：常染色体异常８例占３３．３％,其中常染色相互易位５例,占２０．８％,２例为世界首报异常核型,「４６,ＸＹ,ｔ（１１;１３）（Ｐ１０;ｑ１０）;４６,ＸＹ,ｔ（１;２）（ｐ２２;ｐ２３）」。性染色体异常５例,点２０．８％,正常核型１１例,占４５．８％。     

三例体细胞染色体异常男性的单倍染色体分析

为了解体细胞异常男性的精子染色体变化情况，对３例有反复流产史的体细胞染色体异常男性单倍染色体进行了分析。其中１例４６，ＸＹ，ｔ（１３；１６），＋１６ｐ病例的精子染色体异常率为７６．３６％；１例４５，ＸＹ，Ｒｏｂ（２２；２２）病例仅见两种异常核型，即２３，Ｘ（Ｙ），－２２，＋Ｒｏｂ（２２；２２）为５８．８２％，２２，Ｘ（Ｙ），－２２为４１．１８％；１例４６，ＸＹ，ＹＰ＋病例发现３类Ｙ染色体核型，即２３，ＹＰ＋、２３，Ｙｐ－、２３，Ｙ；Ｘ染色体无变化。上述结果表明相互平衡易泣染色体携带者的精子染色体变化类型较复杂；罗伯逊易位携带者的精子染色体变化较简单；而Ｙ染色体短臂增加者的精子染色体变化有３类，并未见有关报道，是否造成有害的遗传效应尚有待进一步结合体细胞、生殖细胞与子代细胞的染色体进行深入研究。     

1;2易位携带者──家系二例

患者　男,３８岁,表型正常。其妻孕４次,第１胎分娩一男婴,现１２岁,生长发育正常。之后,人工流产２次。第４胎孕６个月时Ｂ超发现胎儿内脏外翻、脊柱裂而行引产。为此,来我院就诊。取夫妇及其子外周血进行染色体核型分析,患者核型为４６,ＸＹ,ｔ（１;２）（ｐ３４;ｑ３１）;其妻核型为４６,ＸＸ;其子核型为４６,ＸＹ,ｔ（１;２）（ｐ３４;ｑ３１）。家族中其他成员无反复流产、死胎及生育畸形儿史。讨论　该父子均为４６,ＸＹ,ｔ（１;２）（ｐ３４;ｑ３１）平衡易位。平衡易位携带者,可产生１８种配子,有１／１８…     

产前诊断染色体平衡易位胎儿一例

产前诊断染色体平衡易位胎儿一例马仁义，王川乐患者男，２６岁。其妻曾自然流产３次，于１９９１年１０月夫妇俩来我室作细胞遗传学检查。抽取夫妇外周血作淋巴细胞染色体检查，Ｇ显带分析核型。患者染色体核型是４６，ＸＹ，ｔ（８；１５）（８ｑ２４．１；１５ｑ２２．...     

2例染色体易位家系中亲代脆性部位表达的研究

本文对２例新发生的Ｘ—常染色体平衡易位携带者家系进行了染色体脆性部位表达的分析。报道了１例患者核型为４６，Ｘ，ｔ（Ｘ；１９）（ｑ２２；ｐ１２）而其母亲ｆｒａ（Ｘ）（ｑ２２）表达频率较高的家系，及患者核型为４６，Ｘ，ｔ（Ｘ；９）（ｑ２６；ｑ２２）其母ｆｒａ（９）（ｑ２２）有表达的病例。此结果提示，染色体断裂点的产生与亲代脆性部位表达增高，特别是在与断裂点同一位点上的脆性部位表达增高有某种联系     

一例46，XX，t（2;10）（q23;q22），t（4;12）（q35;q2103）

一例４６，ＸＸ，ｔ（２；１０）（ｑ２３；ｑ２２），ｔ（４；１２）（ｑ３５；ｑ２１０３）龙志高李麓芸夏家辉患者女，３５岁。智力正常，结婚５年，自然流产１次。体查：生长发育正常，表型正常。细胞遗传学检查：外周血淋巴细胞培养，Ｇ显带，核型为４６，ＸＸ，ｔ（...     

两种不同的t（2；14）易位伴流产

两种不同的ｔ（２；１４）易位伴流产谭凤钦，刘杰，于艳霞例１男，２７岁，婚后３年中妻子３次孕５０＋天自发流产。夫妇临床未查出异常。细胞遗传学检查：妻子核型正常。患者核型为４６，ＸＹ，ｔ（２；１４）（２ｐｔｅｒ→２ｑ１４∷１４ｑ３１→１４ｑｔｅｒ；１４ｐ...     

3例平衡易位携得所致习惯性流产的遗传效应分析

本文报告了３例习惯性流产患者的异常染色体核型,１例,４５,ＸＸ,ｔ（１３ｑ;１４ｑ）、１例,４６,ＸＸ,６（１６;１７）;１例４６,ＸＹ,ｔＺ（１４;２０）,并对其发生机理和遗传效应进行了分析。     

Detection of human chromosomal abnormalities using a new technique combining 4',6-diamidino-2-phenyl-indole staining and image analysis

Chromosomal abnormalities are associated with a variety of diseases. We have developed a new technique for detecting chromosomal abnormalities, and the technique combines conventional 4',6-diamidino-2-phenyl-indole staining (DAPI) with image analysis. The image analysis consists of two simple steps: deconvolution and three-dimensional reconstruction. The technique has been reported for analyzing plant chromosomes but has not been applied to analyze human chromosomes yet. To test the technique, we analyzed five translocations: 46,XX,t(3;21)(12;18), 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7). The results showed that the karyotype of the 46,XX,t(3;21)(12;18) was 46,XX,t(3;21)(q11.1;p13),t(12;18) (q21.2;q23), and the karyotypes of the 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7) were 46,XX,t(11;22)(q23;q12.1); 46,XY,t(7;22)(q32;q13.2); 46,XY,t(11;18)(q13.3;q23), and 46,XY,t(3;7)(q22.1;p13), respectively. The identity of derivative chromosomes involved in the translocations was verified by chromosome painting as well as FISH analyses with centromere probes. The new technique has two advantages: the procedure is simple and convenient, and the results are accurate. The technique has the potential to be used in cytogenetic studies and clinical diagnosis of human diseases in the future.     

Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophilia. Report of two cases.

Two cases are described with the rare combination of inv(16)(p13q22), strongly associated with acute myelomonocytic leukemia with eosinophilia, M4Eo, and the Philadelphia translocation, t(9;22)(q34;q11), hallmark of chronic myeloid leukemia (CML) and rarely found, (less than 1%), in acute nonlymphocytic leukemia. The patients were: case 1, a 9-year-old girl presenting with a white blood cell count (WBC) 42 x 10(9)/L with 32% blasts and bone marrow with blasts and eosinophil precursors consistent with M4Eo, and case 2, a 25-year-old man with WBC 34.7 x 10(9)/L with 13% blasts and bone marrow with features of M4Eo and basophilia. Both patients achieved remission but died following bone marrow transplantation in first remission (case 1) or in relapse (case 2). Cytogenetic findings were: case 1, at diagnosis, 46,XX,inv(16)(p13q22)(21)/46,XX,t(9;22) (q34;q11),inv(16)(8)/46,XX(10), and case 2, at diagnosis, 46,XY,t(9;22) (q34;q11),inv(16)(p13q22) (16) and in remission, 46,XY,t(9;22)(q34;q11) (1)/46,XY (24). Investigation of the breakpoint on 22 in case 1 with Southern blotting and the polymerase chain reaction demonstrated the presence of a p190 mRNA and a breakpoint typical of acute leukemia. Thus a diagnosis of M4Eo was supported by clinical and cytogenetic sequelae in each case; the Ph in case 1 was apparently secondary to inv(16), in case 2 the Ph probably preceded inv(16) in the etiology of the leukemia.     

Multiple apparently unrelated clonal chromosome abnormalities in a squamous cell carcinoma of the tongue

We have cytogenetically examined short-term cultures from a squamous cell carcinoma of the tongue, a tumor type in which chromosome aberrations hitherto have not been reported. No less than 12 pseudodiploid clones were detected, giving the tumor karyotype 46,X,der(X)t(X;1)(q26;p32),der(1)(Xqter→Xq26::1p32→cen→1q42:),del(13)(q11q21),t(15;?) (q26;?)/46,XX,t(1;?)(p34;?),inv(2)(p21q11)/46,XX,t(1;10)(p32;q24)/46,XX,+der(1)(12pter→ 12p11::1p11→cen→1q32::11q13→11q32→1q42:),del(11)(q13q22), - 12, der(17)t(1:17) (q42;p13)/46,XX,inv(1)(p22q44)/47,XX,del(1)(q32),der(17)t(1:17)(p22;q25),der(1)inv(1) (q25q44)t(1;17)(p22;q25),ins(14;7)(q11;q22q36), + 14/46,XX,t(1;4)(q23;q35)/46,XX,t(1;21) (q25;q22),t(2;10)(q31;q26),t(22;?)(q12;?)/46,XX,del(1)(q32)/46,XX,t(1;8)(q44;q21)/46,XX, t(2;21)(q11;p11)/46,XX,t(9;11)(q34;q13). The large number of apparently unrelated abnormalities leads us to suggest that the carcinoma may have been of multiclonal origin.     

Complex chromosome 9, 20, and 22 rearrangements in acute lymphoblastic leukemia with duplication of BCR and ABL sequences

Cytogenetic analysis was performed on bone marrow cells from a 28-year-old woman who was diagnosed with acute lymphoblastic leukemia (ALL). Her karyotype was: 46,XX,t(9;22)(q34;q11)[6]/47, XX,+8,t(9;22)(q34;q11)[4]/47,XX,+8,t(9;22)(q34;q11),del(20)(q11)[2]/46, XX,t(9;22)(q34;q11),del[20](q11)[7]/45,XX,der(9)t(9;22)(q34;q11),-20,-22 , +mar1[8]/45,XX,der(9)t(9;22)(q34;q11),-20,-22,+mar2[3]. Both marker chromosomes are dicentric and have the same size and banding pattern but different primary constrictions. Fluorescence in situ hybridization (FISH) demonstrated that both markers were derived from chromosomes 9, 20, and 22. FISH with the bcr/abl probe showed fusion of the BCR gene with the ABL gene; however, this fusion signal was present in duplicate on both marker chromosomes. To our knowledge, duplication of the BCR/ABL fusion signal on a single chromosome arm has not been reported before, except for the extensive amplification of BCR/ABL fusion signals in the leukemic cell line K-562. These data demonstrate that the marker chromosomes are the result of complex genomic rearrangements. At the molecular level, the BCR/ABL fusion gene encodes the p190 fusion protein. Similar findings have never been observed in any case of ALL.     

Multiple unrelated clonal chromosome abnormalities in an in situ squamous cell carcinoma of the skin

We have cytogenetically analyzed short-term cultures from an in situ squamous cell carcinoma of the skin (Bowen's disease). The following mosaic tumor karyotype was found: 46,XX, -1, +der(1)(pter----p22::q11----cen----p22:), -9, +der(9)t(1;9)(q11; p24)/46,XX,t(3;6) (q21;p21)/46,XX,t(5;14)(q13;q24),t(7;18)(q32;q11)/46,XX,t(8;11)(p22;q13) /46, XX,t(8;11) (p22;q13),t(15;17) (q13;q24)/46,XX,t(12;15)(q12;p11). None of the rearrangements correspond to previously known cancer-associated abnormalities. Two of the clones are obviously related, and it is reasonable to assume that the t(15;17) developed as an evolutionary change in a cell that already contained t(8;11)(p22;q13). Since five clones without cytogenetic similarities were found in this in situ skin carcinoma, we suggest that the tumor was of polyclonal origin. It is impossible to decide whether all, or indeed any, of the visible abnormalities constitute pathogenetically essential primary changes, or merely represent chromosomal markers of secondary importance in tumorigenesis.     

Two new chromosomal abnormalities in chronic myelogenous leukemia 46,XY,t(9;15;22)(q34;q22;q11) and 46,XY,t(6;9;12;22)(p21;q34;q24;q11)

Two new variant cases of chronic myelogenous leukemia (CML) are presented. The first case is a 19-year-old male with a 46,XY,t(9;15;22)(q34;q22;q11) karyotype. The second case is a 75-year-old man with a 46,XY,t(6;9;12;22)(p21;q34;q24;q11) karyotype. In both cases, the prognosis was no different from those cases of CML with the standard t(9;22) as the only abnormality. We recommend that all unusual translocations be reported.     

Cytogenetic subtype involving chromosome 13 in lipoma. Report of three cases

We report three lipomas with rearrangements of chromosome 13. The karyotype of the tumors studied were 45,XX,-8,+der(8)t(8;13)(q22;q12),del(10)(p12),-13; 46,XY,del(13)(q12q22), and 46,XY,t(11;12)(q23;q13),del(13)(q12q22), respectively, revealing common involvement of band 13q12 in the rearrangement. Three other lipomas with aberrations of bands 13q12-q13 have been reported, suggesting that such tumors with abnormalities of chromosome 13 could represent a subgroup of lipoma in addition to those already reported with abnormalities of chromosomes 12q and 6p. The rearrangements of #13 in all these cases also involved loss of the band 13q14 to which the antioncogene associated with retinoblastoma and osteosarcoma is localized. Detailed clinical, histopathologic, and molecular studies should help to further characterize the various cytogenetically defined subgroups of lipoma.     

自然流产夫妇中新发现的四例世界首报核型

目的　分析自然流产与染色体异常的关系。方法　运用外周血淋巴细胞培养法检测自然流产夫妇双方的染色体核型。结果　发现 4种新的平衡易位的人类染色体异常核型 ,分别为 46 ,XX ,t(1 ;6) (q31 ;p2 5) ;46 ,XX ,t(4;5) (q2 5 ;p1 3) ;46 ,XY ,t(5 ;1 5) (p1 3 ;q1 5) ;46 ,XY ,t(1 0 ;1 1 ) (p1 3 ;q2 1 ) ,经鉴定确定为世界首报核型。结论　染色体异常是导致自然流产的原因。     

Chromosomal anomaly of 6q in chronic myelogenous leukemia (CML)

Anomalies of chromosome 6q, along with other chromosomal anomalies, are described in the bone marrow cells of two patients with chronic myelogenous leukemia (CML). One patient, a 14-year-old male, developed the karyotype 46,XY,t(1;6)(p36;q15),del(3)(q25),del(17)(p11),? inv(17)(q12q24) during blastic crisis of his disease. The other patient, a 24-year-old male, had the karyotype 46,XY,del(6)(q13),t(9;22)(q34;q11) during the early phase of his disease and evolution of i(17q) in the karyotype late in the disease.     

染色体复杂重排的细胞遗传学检测及遗传咨询

目的 以4例染色体复杂重排新核型的确诊为例,探讨这类染色体异常的检测方法及遗传咨询。方法 应用常规G显带技术分析4例复杂易位患者的染色体核型,其中2例为智力低下患者,另2例来自有自然流产史的夫妇。2例智力低下患者应用FISH和CGH技术进一步分析并检测其父母核型。查询相关数据库检索4例核型的发生率。结果 4例患者的核型分别为46,XYqh+,t(1;12;2;10)(q25;q11;p14;p11),inv(1)(p22q25),46,XY,t(7;21;8)(p13;q22;p21),46,XX,t(3;7;10)(q28;p15;q22)和46,XY,t(2;16;5)(q33;p12;q33)。2例有智力低下患者经FISH和CGH检测未发现其他染色体的异常,未见染色体微小重复或缺失。4例核型均为国内外文献未曾报道的新核型。结论 染色体复杂重排的遗传学检测需要综合考虑多种核型分析方法的结果,染色体复杂重排的遗传咨询需要着重结合其重排类型和临床症状进行分析。