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Human Genetics

, Volume 104, Issue 4, pp 315–325 | Cite as

The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells

  • D. Gisselsson
  • Mattias Höglund
  • Fredrik Mertens
  • Bertil Johansson
  • Paola Dal Cin
  • Herman Van den Berghe
  • William C. Earnshaw
  • Felix Mitelman
  • Nils Mandahl
Original investigation

Abstract

Acquired ring chromosomes have been found in most types of human neoplasia, with a frequency approaching 10% in malignant mesenchymal tumours. In this study, the composition and dynamics of ring chromosomes were analysed in eight cases of acute myelogenous leukaemia, 17 solid tumours, and five cases with constitutional rings. Chromosomal banding and fluorescence in situ hybridisation were performed to determine the content and the structural heterogeneity of the rings. Telomeric repeats were detected using peptide nucleic acid probes or primed in situ labelling, whereas centromeric activity was evaluated by detection of kinetochore proteins. Mitotic instability was assessed by the frequency of anaphase bridges. The results suggest that human ring chromosomes can be structurally and functionally divided into two categories. In the first of these, size variation is minimal and rearrangement at cell division is uncommon. The majority of such rings contain subtelomeric sequences. Constitutional ring chromosomes and most rings in leukaemias belong to this group, whereas only a few mesenchymal tumours exhibit rings of this type. The second category consists of rings with amplified sequences, primarily from chromosome 12, characteristically occurring in atypical lipomatous tumours and other subtypes of low or borderline malignant mesenchymal neoplasms. Variation in size and number is extensive, and breakage-fusion-bridge events occur at a high frequency. Abnormalities in pericentromeric sequences are common and, in some cases, kinetochores assemble in the absence of alphoid DNA. We conclude that it is not only the ring structure per se or the neoplastic nature of the host cell that determines ring instability, but probably also the functional role of the genes carried in the ring.

Keywords

Acute Myelogenous Leukaemia Peptide Nucleic Acid Telomeric Repeat Ring Chromosome Kinetochore Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • D. Gisselsson
    • 1
  • Mattias Höglund
    • 1
  • Fredrik Mertens
    • 1
  • Bertil Johansson
    • 1
  • Paola Dal Cin
    • 2
  • Herman Van den Berghe
    • 2
  • William C. Earnshaw
    • 3
  • Felix Mitelman
    • 1
  • Nils Mandahl
    • 1
  1. 1.Department of Clinical Genetics, Lund University Hospital, SE-221 85 Lund, Sweden e-mail: david.gisselsson@klingen.lu.se, Tel.: +46-46-17-33-98, Fax: +46-46-13-10-61SE
  2. 2.Center for Human Genetics, University of Leuven, Herestraat 49, B-3000 Leuven, BelgiumBE
  3. 3.Institute of Cell and Molecular Biology, University of Edinburgh, Swann Building, King’s Buildings, Mayfield Road, Edinburgh EH9 3JR, UKGB

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