Chromosomes 17 and 22 involved in marker formation in neurofibrosarcoma in von Recklinghausen disease

Summary We describe the cytogenetic findings in a recurrent neurofibrosarcoma in a patient with nonfamilial von Recklinghausen disease. The composite karyotype was: 40,Y,-X,+dic r(X;20)(:Xp22.2q26::20p13 q13:), -1, +der(1)t(1;3) (p21;p24),-3,-4,-5,+der(5) t(5;?)(q31;?),-9,-9,+der(9)t(3;9)(q21 or q13;p24 or p22), -11,+der(11)t(11;?)(q22.2;?), -17,+der(17)t(17; 22;?)(q21;q13.1;?), -20, -21, -22, -22, +der(22)t(17; 22;?)(q21;q13.1;?),t(2;10)(q37;q22). The derivative chromosomes were demonstrated at the 500 band level. Chromosomes 17 and 22 were shown to be involved in an unbalanced three-way translocation: t(17;22;?)(q21;q13.1;?). This event was confirmed by in situ hybridization, using two probes mapped to chromosome 17. Hill H is a probe derived from the novel oncogene TRE and is located at 17q12–22. The second probe, derived from the granulocyte colony-stimulating factor (G-CSF), is located at 17q11–q21. The rearrangement between chromosomes 17 and 22 showed breakpoints similar or close to the gene loci for neurofibromatosis 1 (NF-1) and NF-2. Based on our observations we recommend that genetic studies on NF-1 tumors include both gene sites (NF-1 and NF-2) rather than focus on one gene locus.     

Complex cytogenetic abnormalities in a patient with chronic myeloid leukemia: a case report

A case of multiple chromosome aberrations in a patient with CML (chronic myeloid leukemia) in the accelerated phase was described. Cytogenetic and molecular genetic studies revealed the presence of a t(9; 22)(q34; q11) translocation and some additional abnormalities such as t(1; 2)(p36; p21), del(6)(q21), +del(8)(q22), del(18)(q21), and +der(22), part of which is not typical for this kind of pathology. The correlation between the obtained data and the data presented in different publications is considered. A probable connection of the detected changes with previously received treatment and a possible effect of these changes on CML progression are discussed.     

9种新的人类染色体异常核型报告

发现９种新的人类染色体异常核型,分别为：４６,ＸＸ,ｔ（２;１０）（ｑ３３;ｑ１１）;４６,ＸＹ,ｔ（１０;１２）（ｑ２６;ｑ２２）;４６,ＸＹ,ｔ（６;１５）（ｐ２３;ｑ２３）;４６,ＸＹ,ｔ（１;６）（ｐ３６;ｑ２１）;４６,ＸＹ,ｔ（１;１９）（ｐ３２;ｐ１３）;４６,ＸＹ,ｔ（１６;１８）（ｑ２２;ｑ２１）;４６,ＸＹ,ｉｎｖ（１）（ｐ３６ｑ２５）;４６,ＸＹ,ｔ（１３;１７）（ｑ１２;ｑ２５）;４６,ＸＹ,ｔ（１５;２１）（ｑ２６;ｑ１１）。异常核型是导致自然流产和不育的原因。     

Two cases of partial trisomy 10q syndrome due to a familial 10;20 translocation

We describe an eleven day-old boy and his first degree double cousin who both have distal trisomy 10q syndrome. Their cytogenetic analysis using GTG-banding showed an unbalanced translocation 46, XY, -20, +der(20), t(10;20)(q22.3, p11) mat and 46, XX, -20, +der(20), t(10;20)(q22.3, p11) mat. The translocation was confirmed by FISH. We have found balanced translocation t(10;20)(q22.3; p11) with cytogenetic and FISH studies in the mothers and maternal grandfather of these children. Our cases had typical craniofacial and visceral anomalies of this syndrome. However case 1 had an agenesia of corpus callosum which was not previously described and case 2 had hypertrophied cardiomyopathy and cliteromegaly which were previously described as rare anomalies for this syndrome.     

19q distal trisomy due to a de novo (19;22)(q13.2;p11) translocation

A 2 4/12-year-old girl whith a de novo 46,XX,-22 + der(22), t(19;22)(q13.2;p11) karyotype is described. From this and other eight similar cases previously published, a typical phenotype in distal 19q trisomy is concluded.     

Familial whole-arm translocations (1;19), (9;13), and (12;21): a review of 101 constitutional exchanges

We report here on 3 familial whole-arm translocations (WATs), namely the 8th instance of t(1;19)(p10;q10) and 2 novel exchanges: t(9;13)(p10;q10) and t(12;21)(p10;q10). The exchanges (1;19) and (12;21) were ascertained through a balanced carrier, whereas the t(9;13) was first diagnosed in a boy with a trisomy 9p syndrome and der(9p13p). Results of FISH analyses with the appropriate α-satellite probes were as follows. Family 1, t(1;19): the D1Z5 probe gave a strong signal on both the normal chromosome 1 and the der(1q19p) as well as a weak signal on the der(1p19q). Family 2, t(9;13): the centromere-9 alphoid and D13Z1/D21Z1 probes under standard stringency gave no signal on the der(9p13p) in both the proband and a carrier brother, whereas the der(9q13q) was labelled only with the centromere-9 alphoid repeat in the latter; yet, this probe under low stringency revealed a residual amount of alphoid DNA on the der(9p13p) in the carrier. Family 3, t(12;21): the D12Z3 probe gave a signal on the normal chromosome 12 and the der(12p21q), whereas the D13Z1/D21Z1 repeat labelled the der(12q21p), the normal chromosome 21, and both chromosomes 13. Out of 101 WATs compiled here, 73 are distinct exchanges, including 32 instances between chromosomes with common alphoid repeats. Moreover, 7/9 of recurrent WATs involved chromosomes from the same alphoid family. Thus constitutional WATs appear to recur more frequently than other reciprocal exchanges, often involve chromosomes with common alphoid repeats, and can mostly be accounted for the great homology in alphoid DNA that favours mispairing and illegitimate nonhomologous recombination.     

一例罕见的复杂易位携带者的染色体绘画研究

本文报道了一例罕见的复杂易位男性携带者,结婚８年,其妻连续７次流产、死胎和出生早夭的畸型儿。用染色体显微切割、ＰＣＲ技术构建的人类７号和８号染色体特异性探针地对其进行了染色体绘画研究,分析确定其核型为：４６,ＸＹ,－７,－８,－９,＋ｄｅｒ（７）、ｔ（７;９）（ｑ２２００;ｐ２４）,＋ｄｅｒ（８）ｉｎｖｉｎｓ（８;７）（ｑ２１００;ｑ３１．２ｑ２２００）,＋ｄｅｒ（９）ｔ（９;７）（ｐ２４;ｑ３１．２）．ｉｓｈｄｅｒ（７）ｔ（７;９）（ｗｃｐ７＋）,ｄｅｒ（８）ｉｎｖｉｎｓ（８;７）（ｗｃｐ７＋,ｗｃｐ８＋）,ｄｅｒ（９）ｔ（９;７）（ｗｃｐ７＋）。染色体绘画技术为研究染色体异常提供了一种有效的分子细胞遗传学技术,本文并对携带者复杂易位的发生机理进行了讨论。     

Revision of the chromosome anomalies of the T-cell malignant cell line peer

A high resolution chromosome banding method was applied to define the karyotype of the PEER cell line. It was found significantly different from that previously described, and can be characterized as follows: 46,XX,-4, del(5) (q21q23), del(6)(q14q22), del(9)(p12p21), i(9p), +der(4) rea(4) involving a large duplication of 4q. The cell cycle duration varies in relation to the time after splitting, slow from 0 to 48 h and faster from 48 to 96 h. The average time found was 25 h with durations of 6 and 15 h for G2 and S-phases, respectively. This variable cell cycle led us to change the conditions of BrdU incorporation to obtain a convenient R-banding. According to our own experience, this can be transposed to many other malignant cells to obtain a high resolution chromosome banding.     

Involvement of the region 13q14 in a patient with adamantinoma of the long bones

Summary A cytogenetic analysis of a lung metastasis of an adamantinoma of the tibia, a rare tumor of the long bones, revealed a karyotype 52, XY, t(7;13)(q32;q14), +7, +12, +13, +19, +der(7) t(7;13), +der(13) t(7;13). The t(7;13) was found to be constitutional in the patient and was also present in peripheral blood lymphocytes of his unaffected father. However, both subjects displayed normal levels of esterase D enzyme activity.     

Karyotype-phenotype analysis: 9p deletion versus 10q2 duplication

An analysis of karyotype-phenotype correlations was carried out on a male infant with 46,XY, -9, +der(9)t(9;10)(p22;q25.2)mat. Cytogenetically, the patient had a 9p deletion and a concurrent 10q2 duplication. Clinically, he manifested predominantly the features of 9p deletion syndrome. An epistasis of 9p deletion over 10q2 duplication was evident in this patient. Possible explanations for this epistatic phenomenon are discussed.     

Clinical and molecular cytogenetic analysis of a rare case of mosaicism for partial monosomy 3p and partial trisomy 10q in human

The results of comprehensive clinical examination and molecular cytogenetic analysis of a patient carrying chromosome 3p+ in 69% of the peripheral blood lymphocytes are presented. Using microdissection of the metaphase chromosomes followed by DOP-PCR, a DNA library specific for the abnormal chromosome was obtained. By fluorescence in situ hybridization (FISH) of this DNA library with chromosomes from the patient and a healthy donor, the aberrant chromosome was identified as der(3)t(3;10)(3p25;q24.3). Since this chromosome was present in only a proportion of patient's cells studied and no chromosome aberrations were revealed in cells of his parents, the der(3)t(3;10) is suggested to appear de novo. The cells carrying der(3)t(3;10) are monosomic for a proportion of 3p25 and trisomic for 10q24.3-->qter. The developmental malformations revealed in the patient, such as the specific features of facial skeleton, mental retardation, microcephaly, and others are similar to those described previously in patients with partial 3p monosomy and 10q trisomy.     

Characteristics of the spontaneously transformed human endothelial cell line ECV304. I. Multiple chromosomal rearrangements in endothelial cells ECV304

Karyotype of endothelial line ECV304 cells obtained from human umbilicus vein endothelial cells was studied using G-banding chromosome staining. It has been revealed that the cells have a polyploidy karyotype with 96-112 chromosomes and multiple numerical and structural clonal rearrangements. Almost all the chromosomes of the karyotype are involved in structural rearrangements. There are several double chromosome rearrangements revealed including del(9)(p21) as well as two derivatives of chromosome 3 with the breakpoint in the locus p25 - der(3)t(3;12)(3p25;12q11- 12q24.?1) and der(3)t(3;?)(3p25). The role of these rearrangements in the immortalization of endothelial cells and sighs of transformation are discussed. In connection with the information received about the fact that the cells of ECV304 line are not endothelial cells but T24, urinary bladder cancer cells (which karyotype was studied by Hurst et al., 2000), the comparative analysis of the karyotypes of these two lines was carried out. It has been revealed that these two lines differ by all cytogenetic characteristics. Neither identical structural chromosomal rearrangements nor cell characteristic of urinary bladder cancer cells were detected. Our line ECV304 is not identical to the line T24.     

Spectral karyotyping of the human colon cancer cell lines SW480 and SW620

The cell lines SW480 and SW620, derived from different stages of colon carcinoma in the same patient, have been used for a number of biochemical, immunological, and genetic studies on colon cancer. A comparative analysis of their karyotypes may identify chromosomal aberrations that might represent markers for metastatic spread. In the present study spectral karyotyping (SKY) was applied to these two colon cancer cell lines. Compared to previously reported G-banded karyotypes, 9 (SW480) and 7 (SW620) markers were identical, 3 (SW480) and 3 (SW620) markers could be redefined, 5 (SW480) and 8 (SW620) markers were newly identified, and 4 (SW480) and 5 (SW620) of the previous described markers could not be confirmed. The redefined aberrations include very complex rearrangements, such as a der(16) t(3;16;1;16;8;16; 1;16;10) and a der(18)t(18;15;17)(q12; p11p13;??) in SW620 and a der(19)t(19;8;19;5) in SW480, that have not been identified by conventional banding techniques. The resulting chromosome gains (5q11-->5q15, 7pter-->q22, 11, 13q14-->qter, 20pter-->p12, X) and losses (8pter-->p2, 18q12-->qter, Y) found in both SW480 and SW620 were in good agreement with those frequently described in colorectal tumors as primary changes in the stem cell. Abnormalities found exclusively in SW620 cells only (gains of 5pter-->5q11, 12q12-->q23, 15p13-->p11, and 16q21-->q24 and losses of 2pter-->2p24, 4q28-->qter, and 6q25-->qter) can be viewed as changes that occurred in a putative metastatic founder cell.     

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3)

We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.     

Sex reversal due to Xp disomy by t(X;Y)(p21;q11).

A 20-month-old infant exhibiting psychomotor retardation, dysmorphisms and ambiguous external genitalia was found to have a 46-chromosome karyotype including a normal X chromosome and a marker Y with most of Yq being replaced by an extra Xp21-->pter segment. The paternal karyotype (G and C bands) was 46,XY. The marker Y composition was verified by means of FISH with a chromosome X painting, an alphoid repeat and a DMD probe. Thus, the final diagnosis was 46,X,der(Y)t(X;Y)(p21;q11)de novo.ish der(Y)(wcpX+,DYZ3+,DMD+). The patient's phenotype is consistent with the spectrum documented in 13 patients with similar Xp duplications in whom sex reversal with female or ambiguous genitalia has occurred in spite of an intact Yp or SRY gene. A review of t(X;Y) identifies five distinct exchanges described two or more times: t(X;Y)(p21;q11), t(X;Y)(p22;p11), t(X;Y)(p22;q11-12), t(X;Y) (q22;q12), and t(X;Y)(q28;q12). These translocations probably result from a recombination secondary to DNA homologies within misaligned sex chromosomes in the paternal germline with the derivatives segregating at anaphase I.     

Clinical and Molecular Cytogenetic Analysis of a Rare Case of Mosaicism for Partial Trisomy 3p and Partial Trisomy 10q in Humans

The results of comprehensive clinical examination and molecular cytogenetic analysis of a patient carrying chromosome 3p+ in 69% of the peripheral blood lymphocytes are presented. Using microdissection of the metaphase chromosomes followed by DOP–PCR, a DNA library specific for the abnormal chromosome was obtained. By fluorescence in situ hybridization (FISH) of this DNA library on chromosomes from the patient and a healthy donor, the aberrant chromosome was identified as der(3)t(3;10)(p25;q24.3). Since this chromosome was present in only a proportion of patient's cells studied and no chromosome aberrations were revealed in cells of his parents, the der(3)t(3;10) is suggested to appear de novo. The cells carrying der(3)t(3;10) are monosomic for a proportion of 3p25 and trisomic for 10q24.3 qter. The developmental malformations revealed in the patient, such as the specific features of facial skeleton, mental retardation, microcephaly, and others are similar to those described previously in patients with partial 3p monosomy and 10q trisomy.     

Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression

We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11-q21, 6q11-q15 and 1p36 (15-77%). SKY detected nine additional sites (1p11-p13, 2p11-p13, 6q21, 8q24, 6q21, 9p13, 10q22-q24, 12q11-q13 and 17q11-q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2-3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13-p21, 2q11-q21, 2q31-q37, 12q12-q15, 17q21-q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11-q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11-p13, 1p36, 1q11-q21, 8q24, 9p13, and 17q11-q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27).