Different clones of t(1;12)/t(12;12) involving the ETV6 gene in a case of acute myeloid leukemia

We report a boy with Down syndrome and leukemia who acquired uniparental isodisomy of chromosome 7q as a secondary chromosomal change during recurrence of the disease. His karyotype before therapy was 46,XY,der(1)t(1;1)(p36;q32),-7,+21c/46,idem,del(9)(p22), whereas at recurrence it was 46,XY,der(1)t(1;1)(p36;q32,-7,der(7)(qter-->p22 through pter::q10-->qter),del(9)(p22),+21c/47,XY,+21c. By using polymerase chain reaction amplification of D7S493 and D7S527 markers, we identified the loss of the maternal chromosome 7 with a consequent paternal isodisomy in the clone with dup7q. This rearrangement could be implicated in the progression of the disease by causing (1) nullisomy for a gene or genes located on 7p22-->pter, (2) functional double doses of exclusively paternal expressed genes, and (3) restoration of the effects produced by haploinsufficiency of biparental expressed genes.     

Noninvolvement of a constitutional heritable fragile site at 10q24.2 in rearranged chromosomes from rectal carcinoma cells

A fragile site in chromosome band 10q24.2 was found in the lymphocytes of a patient ascertained for rectal carcinoma. The karyotype of 110 R-banded tumor cells was performed, showing two stemline formulas: 46,XXY,-1,-18,+20,der(6),t(1;6)(q21.1;q22.3),i(17q) and 46,XY,-1,-18,+8,+20,der(6),t(1;6),del(2)(p1600p22),i(17q). These findings are in agreement with our previous studies, which reported that the rearrangement of chromosome #17 and the loss of chromosome #18 are recurrent anomalies in colorectal carcinomas. In addition to these rearrangements, other anomalies were occasionally observed in tumor cells, but no breakages nor rearrangements involving band 10q24.2. The relationships between fragile sites and cancer breakpoints are discussed.     

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.     

Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation

A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart.     

Karyotypic evolution in acute myelomonocytic leukemia with pericentric inversion of chromosome 16

A 37-year-old Japanese male patient with acute myelomonocytic leukemia subtype M4 (according to FAB classification) associated with bone marrow eosinophilia and specific chromosome abnormalities: a pericentric inversion of chromosome 16, inv(16)(p13q22); a long arm deletion of chromosome #7, del(7)(q22q34); and a gain of chromosomes #8 and #22 is reported. In addition to the modal karyotype, 47,XY,7q-,inv(16),+22, there were three other clones whose karyotypes were 46,XY,inv(16); 47,XY,inv(16),+22; and 48,XY,+8,inv(16),+22. As these karyotypes were related to each other, the presence of multiple clones indicated that karyotypic evolution had occurred. The karyotypic evolution associated with 7q- has not been reported previously in patients with M4Eo with inv(16).     

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.     

Rearrangement of the MLL gene in acute myeloblastic leukemia: report of two rare translocations

Band 11q23 is known to be involved in translocations and insertions with a variety of partner chromosomes. They lead to MLL rearrangement, resulting in a fusion with numerous genes. We report here 2 male adults in whom a diagnosis of acute myelomonoblastic leukemia (FAB M4) and acute monoblastic leukemia (FAB M5) was made. Conventional cytogenetic techniques showed a 45,XY,t(1;11)(p32;q23),-7 karyotype in the first case and a 46,XY, t(11;17)(q23;q21) in the second case. Fluorescent in situ hybridization (FISH) with a specific MLL probe showed the gene to be disrupted, the 3' region being translocated on the derivative chromosomes 1 and 17, respectively. Fourteen and 24 patients, including ours, with acute myeloblastic leukemia associated with a t(1;11)(p32;q23) and a t(11;17)(q23;q21), respectively have been reported in the literature. Several patients with the latter translocation have also been identified to have acute lymphoblastic leukemia (ALL). Although both translocations are preferentially associated with monocytic differentiation, the t(11;17)(q23;q21) is more common in adults and has been reported in many patients with ALL, compared to the t(1;11)(p32;q23).     

Disappearance of a highly unusual clone, 46,XY,del(7)(p12),t(9;22)(q34;q11) in chronic myeloid leukemia after treatment with recombinant interferon and cytosine arabinoside.

A patient with the typical features of the stable phase of chronic myeloid leukemia (CML) displayed two karyotypically related subclones. In addition to the t(9;22), cells from one clone contained a deletion of the short arm of chromosome 7, del(7)(p12), [46,XY,del(7)(p12),t(9;22)(q34;q11)]; the other contained only the standard translocation [46,XY,t(9;22)(q34;q11)]. Cells with a deletion of the short arm of chromosome 7 at band p12 as the only additional abnormality have not been observed previously in CML. Conventional chemotherapy with hydroxyurea and then with recombinant interferon-alpha (rIFN-alpha) did not reduce the population of either subclone. However, after treatment with a combination of rIFN-alpha and low-dose cytosine arabinoside (LoDac) continuously infused subcutaneously (s.c.), cells from the clone with the deleted chromosome 7 disappeared and normal metaphases were demonstrable.     

A de novo complex chromosomal rearrangement with a translocation 7;9 and 8q insertion in a male carrier with no infertility

A de novo complex chromosomal rearrangement (CCR) involving chromosomes 7, 8 and 9 in a male carrier was ascertained through his healthy wife's recurrent spontaneous abortions. Six pregnancies over eight years resulted in four spontaneous abortions and two livebirths who died perinatally due to abnormal vital signs. Cytogenetic analyses utilizing high resolution chromosome banding technique showed a deletion of band in a der(7) chromosome and an extra band inserting at 8q21.2. Another extra band was also observed at the band 9p24, but it could not be karyotypically determined. Fluorescent in-situ hybridization using chromosome 7 and 8 specific microdissected library as probes confirmed the insertion of a segment from the translocated chromosome 7 into a chromosome 8, and additionally revealed a translocation between chromosomes 7 and 9. The karyotype of the CCR carrier was determined as 46,XY,t(7;9)(q22;p24),ins(8;7)(q21.2;q22q32).ish der(9)(wcp7+);ins(8;7)(wcp8+,wcp7+). Comparing with previously reported male CCR carriers with our case, we conclude that male CCR carriers may not always present with infertility or subfertility phenotypes. This may suggest that rare transmission of male carriers could result from abnormal chromosomal rearrangements during meiosis and gametogenesis in addition to frequent infertility.     

Two cases of acute promyelocytic leukemia with variant translocations: the importance of chromosome No. 17 abnormality

Two patients with acute promyelocytic leukemia (APL) were found to have chromosomal translocations in their leukemic cells; one had a 46,XX,t(7;17)(q36;q22) and another a 46,XY,t(1;17)(p36;q21) karyotype. These two cases of APL seem to be the first involving variant translocations instead of the standard t(15q+; 17q-) translocation. The present cases strongly suggest that the rearrangement of chromosome #17, which occurs in bands of the q21-22 region of the long arm, is crucially important in the pathogenesis of APL.     

Characterization of t(11;19)(q23;p13.3) by fluorescence in situ hybridization analysis in a pediatric patient with therapy-related acute myelogenous leukemia

This case presents a Caucasian girl diagnosed with early pre-B cell acute lymphoblastic leukemia at age 2 years. The only chromosomal anomaly detected in her bone marrow cells at this time was an add(12p). By age 4 years, she had a bone marrow and central nervous system (CNS) relapse of ALL and was treated with chemotherapy that included etoposide. She was in complete remission for 2 years following chemotherapy with etoposide, but later developed therapy-related acute myeloid leukemia (t-AML). At this time, a t(11;19)(q23;p13.3) rearrangement was detected in her bone marrow cells. The AML relapsed again 1 year after allogeneic bone marrow transplant (BMT). The presence of a chromosome 11 abnormality involving band 11q23 in this patient suggests that the transformation from ALL to t-AML was a consequence of etoposide included in her chemotherapy. Studies have shown that the 11q23 breakpoint in the t(11;19) rearrangement is consistent, and involves the MLL gene in t-AML patients. However, the breakpoint in 19p is variable in that it could be located either at 19p13.1 or 19p13.3 and thus could involve either of two genes: ELL (11-19 lysine-rich leukemia gene) on 19p13.1 or ENL (11-19 leukemia gene) on 19p13.3. In this study, the t(11;19)(q23;p13.3) was further characterized and the breakpoint regions were defined by fluorescence in situ hybridization (FISH) analysis.     

Complex translocation involving chromosomes #1, #9, and #22 in a patient with chronic myelogenous leukemia

A case of Philadelphia chromosome positive chronic myelogenous leukemia with a complex translocation involving chromosomes #1, #9, and #22 is described. All cells in the bone marrow showed this rearrangement, and Q-banding analysis showed the predominant karyotype to be 46,XY, t(1;9;22)(p22;q34;q11).     

Cytogenetic study of malignant triton tumor: a case report

Malignant triton tumor (MTT) is a highly malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. Few cytogenetic studies of MTT have been reported using conventional cytogenetic analysis. Here, we report a comprehensive cytogenetic study of a case of MTT using G-banding, Spectral Karyotyping(), and fluorescence in situ hybridization (FISH) for specific regions. A complex hyperdiploid karyotype with multiple unbalanced translocations was observed: 48 approximately 55,XY,der(7)add(7)(p?)dup(7)[2],der(7) t(7;20)(p22;?)ins(20;19)[5],der(7)ins(8;7)(?;p22q36)t(3;8)t(8;20)[15],-8[5],-8[19],r(8)dup(8), +der(8)r(8;22)[4],-9[9],der(11)t(11;20)(p15;?)ins(20;19)[22],der(12)t(8;12)(q21;p13)[21],der(13) t(3;13)(q25;p11),-17,-19,der(19)t(17;19)(q11.2;q13.1),-20,-22,+4 approximately 7r[cp24]/46,XY[13]. The 1995 International System for Human Cytogenetic Nomenclature was followed where possible. Note that breakpoints were frequently omitted where only SKY information was known for a small part of an involved chromosome. Our analysis revealed some breakpoints in common with those previously reported in MTT, MPNST, and rhabdomyosarcoma, namely 7p22, 7q36, 11p15, 12p13, 13p11.2, 17q11.2, and 19q13.1. FISH showed high increase of copy number for MYC and loss of a single copy for TP53.     

Chromosome abnormalities and rare fragile sites detected in azoospermia patients

Summary We have examined constitutional chromosome abnormalities and fragile sites in 40 patients with azoospermia. Chromosome abnormalities were found in four cases. Three cases showed a deletion of the long arm of the Y chromosome 46,X,del(Yq) and the other case had a ring of G group chromosome 46,XY,r(G). In a rare fragile sites test, four fragile site carriers were detected and three rare autosomal fragile sites were identified; fra(8)(q24.1), fra(11)(p15.1), and fra(17)(p12). The expression of these fragile sites were induced specifically by AT-specific DNA ligands, such as distamycin A and Hoechst 33258. In addition, one patient was found to be the case of double ascertainment of fragile sites, fra(8)(q24.1) and fra(17)(p12). The overall frequency of distamycin A-inducible fragile sites in azoospermia patients appeared to be higher than those reported for Japanese healthy subjects and cancer patients. However, no significant relation among fragile sites, clinical and histological findings has been detected so far.     

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。     

应用染色体涂染技术检测慢性粒细胞白血病少见Ph易位的初探

为了对４例先经染色体Ｒ显带检查，初步诊断为少见Ｐｈ易位的慢性粒细胞白血病（ＣＭＬ）患者的骨髓染色体异常，又采用染色体涂染技术作了进一步研究。结果显示，２例为简单变异易位，核型分别是４６，ＸＸ，ｔ（５；２２）（ｑ３４；ｑ１１）和４６，ＸＸ，ｔ（１９；２２）（ｑ１３；ｑ１１）；１例为隐匿易位，核型是４６，ＸＹ，ｔ（１；２２）（ｑ４１；ｑ１１）；另１例为涉及３条染色体异常的复杂易位，核型是４６，ＸＹ，ｔ（７；９；２２）（ｑ３１；ｑ３４；ｑ１１）。本研究表明，染色体涂染技术可作为显带染色体检测ＣＭＬ少见Ｐｈ易位的一种辅助手段     

Cryptic duplication of the distal segment of 22q due to a translocation (21;22): three case reports and a review of the literature

Duplications of the proximal segment of chromosome 22q are not uncommon, like Cat-eye syndrome and duplications due to familial (11;22) translocations. However, duplications of the distal long arm of chromosome 22 (22qter) seem to be exceedingly rare. So far, duplications of 22q12 or 22q13 to 22qter have been described in 21 patients, of whom 13 had a pure duplication 22qter. Here we report on three new cases with a pure duplication of the distal part of 22q. The first patient carries a duplication of terminal 22q due to a de novo unbalanced translocation, 46,XX,der(21)t(21;22) (p13;q13.2), detected by NOR-staining, while the other patients have a familial cryptic duplication of terminal 22q due to an unbalanced translocation, 46,XY,der(21)t(21;22)(p10;q13.3). The last two patients were initially thought to have a polymorphic variant of 21p, but additional subtelomeric screening using FISH showed the extra material was derived from chromosome 22. Terminal duplications of 22qter may be more common than generally assumed, but due to its small size, especially when located on an acrocentric chromosome and/or possibly relatively mild phenotype remain undetected thus far.     

Cytogenetic abnormalities in an ossifying fibroma from a patient with bilateral retinoblastoma.

Cytogenetic analysis of a cemento-ossifying fibroma from a patient with nonfamilial bilateral multicentric retinoblastoma revealed three reciprocal translocations with the karyotype 46,XY,t(1;18)(q21;q21.3),t(3;10)(p13;q22),t(6;11)(p22;p15). Routine and high-resolution cytogenetic analysis of peripheral blood leukocytes showed an apparently normal, 46,XY chromosome pattern with no deletion of chromosome 13. Molecular analysis demonstrated no gross differences in the retinoblastoma gene or the TP53 gene between constitutional and tumor DNA. This is the first cytogenetic analysis of a cemento-ossifying fibroma and the first report of this tumor in a retinoblastoma patient. The data may be added to the small, but growing literature on cytogenetic aberrations in benign tumors and may lend insight into genes involved in cell proliferation and neoplastic transformation.     

Nonrandom chromosome changes in Kaposi sarcoma: cytogenetic and FISH results in a new cell line (KS-IMM) and literature review

The karyotype of a new tumorigenic Kaposi sarcoma (KS)-derived cell line, as defined by cytogenetic and fluorescence in situ hybridization (FISH) analysis is 49,XY,i(1)(q10),i(7)(p10),+i(7) (q10),+der(8)t(8;13)(p11;q11),-13,+del(14)(q22),+der(17)t(1;17)(p13;p13). Our aim was to point out some characteristics and recurrent chromosome changes probably playing a relevant role in the malignant progression of KS, by a comparison of the cytogenetic results obtained in the present study with data from the literature. The interpretation of the cytogenetic results is that KS development occurs by multiple steps: an initial reactive polyclonal cell proliferation is associated with chromosome instability; the cells in a later stage acquire clonal chromosome changes. If many chromosome changes are present, particularly 8q and 1q trisomy, 3p14-->pter deletion, 1p13, 13p14.3, 7q22, 8p11, 13q11, and 19q13 band rearrangements, KS acquires a neoplastic aggressive state.