Karyotypic Changes (karyotypic + change)

Distribution by Scientific Domains

Selected Abstracts

Detection of a t(1;22)(q23;q12) translocation leading to an EWSR1-PBX1 fusion gene in a myoepithelioma

Petter Brandal
Chromosome banding as well as molecular cytogenetic methods are of great help in the diagnosis of mesenchymal tumors. Myoepithelial neoplasms of soft tissue including myoepitheliomas, mixed tumors, and parachordomas are diagnoses that have been increasingly recognized the last few years. It is still debated which neoplasms should be included in these morphologically heterogeneous entities, and the boundaries between them are not clear-cut. The pathogenetic mechanisms behind myoepithelial tumors are unknown. Only five parachordomas and one mixed tumor have previously been karyotyped, and nothing is known about their molecular genetic characteristics. We present a mesenchymal tumor classified as a myoepithelioma that had a balanced translocation t(1;22)(q23;q12) as the sole karyotypic change. A novel EWSR1-PBX1 fusion gene consisting of exons 1,8 of the 5,-end of EWSR1 and exons 5,9 of the 3,-end of PBX1 was shown to result from the translocation. Both genes are known to be targeted also by other neoplasia-specific translocations, PBX1 in acute lymphoblastic leukemia and EWSR1 in several solid tumors, most of which are malignant. Based on the structure of the novel fusion gene detected, its transforming mechanism is thought to be the same as for other fusion genes involving EWSR1 or PBX1. © 2008 Wiley-Liss, Inc. [source]

Isotype class switching and the pathogenenesis of multiple myeloma

J. A. L. Fenton
Abstract Translocations at the immunoglobulin heavy chain locus (14q32) are now considered the commonest karyotypic change in multiple myeloma. These translocations are thought to be intimately involved in the pathogenesis of this disease. The heavy chain locus is strongly transcriptionally active in B and plasma cells and transfer of a potential oncogene to 14q32 would result in its dysregulation. Molecular characterization suggests that the majority of these breakpoints cluster in switch regions within the heavy chain locus. Switch regions are normally involved in the regulated process of isotype switching so that in myeloma the rearrangements are believed to be a result of so-called illegitimate (aberrant) switch recombination and are likely to be an early event in myeloma development. A legitimate switch recombination event occurs between two switch regions producing a hybrid switch; this is necessary for class switching to proceed on a productive allele. In this review we describe the process of isotype switching and how illegitimate class switching may be related to the pathogenesis of multiple myeloma. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Shwachman,Diamond syndrome with late-onset neutropenia and fatal acute myeloid leukaemia without maturation: a case report

Jean-François Lesesve
Abstract: We report on a male patient affected by Shwachman Diamond syndrome (SDS) who presented an unusual delayed neutropenia and then developed a poorly differentiated acute myeloid leukaemia (M0-AML) with trilineage myelodysplasia in adulthood. Conventional cytogenetics revealed complex karyotypic changes (monosomies 20, 21, 22, additional 15p). The patient was treated with conventional chemotherapy but never reached complete remission of leukaemia and died 18 months after diagnosis. SDS is an inherited bone marrow failure syndrome with a high propensity to leukaemic transformation. Since neutropenia may be intermittent or with delayed onset, and leukaemic transformation may not occur until adulthood, full blood count should be regularly monitored in such patients. [source]

PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL with complex chromosomal rearrangements,

Bruce Poppe
We present an extensive characterization of 10 B-cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M-FISH). Pathologic and clinical review revealed the presence of this rearrangement in 4 histiocyte-rich, T-cell-rich B-cell lymphomas (HRTR-BCLs) and 2 posttransplantation diffuse large B-cell lymphomas (PTLD-DLBCLs). In contrast to initial observations describing this translocation in lymphoplasmacytic lymphoma (LPL) and LPL-derived large B-cell lymphoma, our data showed a wide morphologic and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an association between this aberration and a subset of de novo DLBCLs presenting with advanced disease and adverse prognosis. In addition, the recurrent incidence of this rearrangement in both HRTR-BCL (4 cases) and PTLD-DLBCL (2 cases) was previously unrecognized and is intriguing. © 2005 Wiley-Liss, Inc. [source]

Assessment by M-FISH of karyotypic complexity and cytogenetic evolution in bladder cancer in vitro

Sarah V. Williams
We carried out multiplex fluorescence in situ hybridization (M-FISH) and follow-up FISH studies on a large series of transitional cell carcinoma (TCC) cell lines and 2 normal urothelium,derived cell lines, several of which have not had karyotypes reported previously. M-FISH analysis, with appropriate follow-up, complements conventional cytogenetic analysis and array CGH studies, allowing a more accurate definition of karyotype. The detailed karyotypic data obtained will assist in choosing suitable cell lines for functional studies and identifies common losses, gains, breakpoints and potential fusion gene sites in TCC. We have shown changes in cell lines RT112 and DSH1 following prolonged culture, and differences in karyotype, between RT112 cultures obtained from different sources. We propose a model for the evolutionary changes leading to these differences. A comparison with the literature found other examples of differences in cell-line karyotypes between different sources. Nevertheless, several karyotypic changes were preserved between different sources of the same cell line and were also seen in more than one cell line. These may be the most important changes and include ,8p, +20, 4q,, 10p,, 16p, and breaks in 8p21. We carried out a more detailed follow-up of some regions, which showed involvement of 8p breaks and losses in 15 of 16 TCC cell lines but in neither of the normal urothelium,derived cell lines. Some changes represented distal loss, whereas others were small deletions. Further study of this region is warranted. Supplementary material for this article can be found on the Genes, Chromosomes and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html. © 2005 Wiley-Liss, Inc. [source]