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Molecular Cytogenetics

Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones

Leukemia volume 15, pages 1193–1202 (2001)Cite this article

Abstract

During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.

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Acknowledgements

We thank Marjorie Isaacson for gathering the data on these patients and Shalini Reshmi for technical assistance. This work was supported by a Grant-in-Aid for International Exchange from Japan Clinical Pathology Foundation (YS), NIH grants CA42557 (JDR) and CA40046 (JDR and MML), The Spastic Paralysis Foundation of the Illinois-Eastern Iowa District of Kiwanis International (JDR) and the G Harold and Leila Y Mathers Charitable Foundation (JDR).

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Authors and Affiliations

  1. Division of Molecular Cytogenetics, Department of Clinical Pathology, Research Institute of International Medical Center of Japan, Tokyo, Japan

    Y Sato

  2. Hematologic Clinic, Saitama Cancer Center Hospital, Saitama, Japan

    H Kobayashi

  3. Department of Pediatrics, Aomori Municipal Hospital, Aomori, Japan

    Y Suto

  4. Department of Medicine, University of Chicago, Section of Hematology/Oncology, Chicago, IL, USA

    HJ Olney, EM Davis, HGill Super, R Espinosa III, MM Le Beau & JD Rowley

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Sato, Y., Kobayashi, H., Suto, Y. et al. Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones. Leukemia 15, 1193–1202 (2001). https://doi.org/10.1038/sj.leu.2402188

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