Jumping Translocation Research Articles

Shortened Telomeres Involved in a Case With a Jumping Translocation at 1q21

The jumping translocation (JT) is a rare chromosomal abnormality in which a specific chromosomal segment translocates onto the ends of various chromosomes (jumps). In most cases, the region distal to 1q21 jumps onto numerous different telomeres. Here we report a molecular study of the JT involving 1q21 found in a patient with acute myelomonocytic leukemia that had transformed from myelodysplastic syndrome (MDS). This is the first report describing the analysis of the molecular structure of the JT. We demonstrated the presence of a stretch of telomeric repeats at the breakpoint by means of a fluorescence in situ hybridization experiment, molecular cloning, and nucleotide sequencing of the fused region. A significant amount of variant telomeric repeats (a telomeric sequence having one-base mismatch within the authentic telomeric repeat TTAGGG) was found in this region. The variant telomeric repeat has been shown to be present in the proximal region of telomeres and does not perform telomeric functions by itself. Therefore, these results indicated that the telomeres had already been critically shortened when the jumps occurred. We suggest that the extended proliferation of cancer cells during the premalignant stage, such as MDS, results in chromosomal instability due to the loss of telomeric functions.

Shortened Telomeres Involved in a Case With a Jumping Translocation at 1q21

AbstractThe jumping translocation (JT) is a rare chromosomal abnormality in which a specific chromosomal segment translocates onto the ends of various chromosomes (jumps). In most cases, the region distal to 1q21 jumps onto numerous different telomeres. Here we report a molecular study of the JT involving 1q21 found in a patient with acute myelomonocytic leukemia that had transformed from myelodysplastic syndrome (MDS). This is the first report describing the analysis of the molecular structure of the JT. We demonstrated the presence of a stretch of telomeric repeats at the breakpoint by means of a fluorescence in situ hybridization experiment, molecular cloning, and nucleotide sequencing of the fused region. A significant amount of variant telomeric repeats (a telomeric sequence having one-base mismatch within the authentic telomeric repeat TTAGGG) was found in this region. The variant telomeric repeat has been shown to be present in the proximal region of telomeres and does not perform telomeric functions by itself. Therefore, these results indicated that the telomeres had already been critically shortened when the jumps occurred. We suggest that the extended proliferation of cancer cells during the premalignant stage, such as MDS, results in chromosomal instability due to the loss of telomeric functions.

Segmental Jumping Translocation in Leukemia and Lymphoma with a Highly Complex Karyotype

In order to identify the oncogene associated with malignant transformation 141 leukemia and malignant lymphoma patients were studied by FISH. Specific chromosome regions were translocated onto structurally abnormal chromosomes, resulting in partial tri-, tetra-, or pentasomy of these regions. We designated this type of chromosomal translocation as a “segmental jumping translocation (SJT)”. These SJTs were found in several chromosomal regions such as 8q24, 9q34, 11q13, 11q23, 13q14, 14q24-q32, 21q22 and 22q11. The SJT at 9q34, which involved the ABL oncogene, was found in three of nine secondary leukemia patients who were treated with anticancer drugs and radiation. Non-Hodgkin's lymphoma and acute myeloid leukemia (AML) patients had 3–7 copies of SJT at 11q13 or 11q23. SJT at 14q32 and 21q22 were predominantly detected in the acute type of adult T-cell leukemia (8 of 27 patients) and in AML (5 of 17 patients). The size of the SJT regions varied among the patients. The overlapping region within the SJT could involve oncogene(s) associated with transformation to the advanced stage in leukemia and lymphoma patients. The SJT provides evidence of a new mechanism for gene amplification and formation of unidentified marker chromosomes in the advanced disease stage.

Fluorescence in situ hybridization assessment of the telomeric regions of jumping translocations in a case of aggressive B-cell non-Hodgkin lymphoma

We report a jumping translocation involving a donor chromosome 1 long arm in a case of aggressive B-cell non-Hodgkin lymphoma (NHL). Conventional cytogenetic banding studies demonstrated a breakpoint distal to the heterochromatic region of the donor 1q chromosome. Characterization by fluorescence in situ hybridization (FISH) of the jumping translocation demonstrated an apparent telomeric sequence loss of the recipient chromosomes. Additional cytogenetic aberrations, including the t(18;22) translocation associated with non-Hodgkin lymphoma, were also observed in this case. Cytogenetically similar cases of jumping translocations reported in the literature have implicated a preferential involvement of the donor chromosomes' heterochromatic regions and the telomeric regions of the recipient chromosomes. Jumping translocations are still considered rare and their appearance is associated with a poor prognosis. The presence of these specific findings for this case are discussed and compared with those previously reported in other hematologic disorders.

Interstitial telomeric sequences at the junction site of a jumping translocation.

The mechanism(s) for the origin of jumping translocations (JTs) are unknown. To assess the possible involvement of telomeric sequences in the jumping process, metaphases of a patient with hydrops fetalis having a JT were analyzed for the presence of interstitial telomeres. Telomere DNA sequences were detected at the junction sites of the donor and the recipient chromosomes. Interstitial telomeric sequences have so far only been detected in JTs involving chromosome 15q in patients with Prader-Willi syndrome. Our finding of interstitial telomeric sequences in a JT with a chromosome different from chromosome arm 15q in a patient without Prader-Willi syndrome implies that telomere sequences may be common to all telomeric JTs. The possible role of telomeric sequences as a cause of the observed chromosomal mosaicism is discussed.

Trisomy 15 rescue with jumping translocation of distal 15q in Prader-Willi syndrome.

We report a patient with Prader-Willi syndrome (PWS) and mosaicism for a de novo jumping translocation of distal chromosome 15q, resulting in partial trisomy for 15q24-qter. A maternal uniparental heterodisomy...

Frequent Jumping Translocations of Chromosomal Segments Involving the ABL Oncogene Alone or in Combination With CD3-MLL Genes in Secondary Leukemias

AbstractSeven secondary leukemia patients were treated for solid tumors or malignant lymphoma with anticancer drugs or radiation. We studied bone marrow samples from these patients by fluorescence in situ hybridization (FISH). Of the seven patients, three had increased signals for the ABL oncogene (9q34) on interphase nuclei and at metaphase. One of the three patients also had four signals for the CD3 (MLL) region (11q23). Whole painting probes revealed that these chromosomal regions were translocated onto structurally abnormal chromosomes, resulting in partial tri-, tetra- or penta-somy of these regions. We called this type of translocation “segmental jumping translocation (SJT).” SJT of the ABL oncogene was not detected in samples from 15 patients with de novo acute myelocytic leukemia (AML), 12 with myelodysplastic syndrome (MDS), or 20 with chronic myelocytic leukemia (CML) at the chronic phase. Furthermore, monosomy 7 was also found in the patients with the gene amplification. These results indicate that SJT of ABL and/or CD3 (MLL) genes is associated with the leukemogenesis of secondary leukemia. The SJT may be one mechanism of gene amplification.

Three Cases of Hematologic Malignancies with Jumping Translocation

Three Cases of Hematologic Malignancies with Jumping Translocation

Jumping translocations of 1q in Burkitt lymphoma and acute nonlymphocytic leukemia

“Jumping translocations” have been observed mostly in cultured cells. Reports of such translocations in hematologic malignancies are few, and the associated clinical picture is unclear. We report three cases of hematologic malignancies with various unbalanced translocations (so-called jumping translocation) involving trisomy of the long arm of chromosome 1. The first case was a 13-year-old boy with Burkitt lymphoma who showed a very aggressive clinical course. The second case was a 10-month-old girl with acute nonlymphocytic leukemia [ANNL, French-American-British (FAB) classification M0] who had high risk factors, including hyperleukocytosis with a peripheral white blood cell (WBC) count of 300,000/μl, and who died 7 months after diagnosis. The third case was a 6-year-old boy with Burkitt-like leukemia whose first remission lasted only 1 month. Only 10 cases with jumping translocations, including two cases with Burkitt-like leukemia/lymphoma, have been reported previously. This rare phenomenon may occur with increased frequency in Burkitt-like leukemia/lymphoma and may be an adverse prognostic factor.

“Jumping translocation” in a 17-month-old child with mixed-lineage leukemia

A 17-month-old child with acute biphenotypic (pre B-ALL/myelomonocytic) leukemia is reported. Extensive cytogenetic analysis performed at various stages of the disease revealed a clonal evolution at the time of initial diagnosis with two types of abnormal clones, one with trisomy 22 and two other related clones with trisomy 22 plus partial trisomy of the long arm of chromosome 1 associated with the telomeric segment of either chromosome 20q or 21p. At the time of relapse the only abnormal clone involved trisomy 22 and partial trisomy of 1q, but this time in association with the telomeric segment of 14p. The unique feature of these translocations is discussed and the possibility of the correlation between the different chromosomal abnormalities and the expression of biphenotypic markers is raised.

Jumping translocation of chromosome 14 in a skin squamous cell carcinoma from a xeroderma pigmentosum patient

The cytogenetic study of a case of cutaneous squamous cell carcinoma developed in a child affected by xeroderma pigmentosum is described. In this paratetraploid tumor, virtually all mitoses had the following rearrangements: i(1q), i(1p), t(3q14q), del(9p), and der(19)t(8;19). In addition, there were several deletions of 1p and 1q. The del(9p) likely occurred as the first rearrangement. The distal segment of the short arm of chromosome #9 and the long arm of #19 and #22 were the most underrepresented and chromosome #6 the most overrepresented chromosome or chromosome segment. The most striking anomaly detected was a jumping translocation of chromosome #14, involved with chromosomes #1, #3, #5, #7, #9, #14, and #22. The breakage of chromosome #14 always occurred on the short arm.