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  • Original Paper
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Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly clustered

Oncogene volume 18, pages 543–550 (1999)Cite this article

Abstract

The inv(16) and related t(16;16) are found in 10% of all cases with de novo acute myeloid leukemia. In these rearrangements the core binding factor β (CBFB) gene on 16q22 is fused to the smooth muscle myosin heavy chain gene (MYH11) on 16p13. To gain insight into the mechanisms causing the inv(16) we have analysed 24 genomic CBFB-MYH11 breakpoints. All breakpoints in CBFB are located in a 15-Kb intron. More than 50% of the sequenced 6.2 Kb of this intron consists of human repetitive elements. Twenty-one of the 24 breakpoints in MYH11 are located in a 370-bp intron. The remaining three breakpoints in MYH11 are located more upstream. The localization of three breakpoints adjacent to a V(D)J recombinase signal sequence in MYH11 suggests a V(D)J recombinase-mediated rearrangement in these cases. V(D)J recombinase-associated characteristics (small nucleotide deletions and insertions of random nucleotides) were detected in six other cases. CBFB and MYH11 duplications were detected in four of six cases tested.

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Acknowledgements

The authors thank Walter Heeroma for help in drafting and O Bruzzese, M Leeman and Dr C Castagné for their assistance in chromosome and FISH analysis of Swiss patients, the clinicians and the members of the Leukemia group (Chairman, U Hess) of the Swiss Institute for Applied Cancer Research/Swiss Group for Clinical Cancer Research for providing the Swiss patients. These studies were supported by the European Community sponsored Biomed concerted action for `Molecular Cytogenetic Diagnosis of Hematological Malignancies' CT941703 and the Dutch Cancer Society. Cytogenetic and FISH analyses performed in Lausanne, Switzerland, were supported by grants from the Ligue Suisse contre le Cancer (FOR 209), the Ligue Agrovienne contre le Cancer, the Cramer Foundation, the Swiss Institute for Applied Cancer Research/Swiss Group for Clinical Cancer Research, Leukemia Group, the Swiss national Science Foundation (31-32319.91), the Recherche Suisse contre le Cancer, and the Stiftung zur Krebsbekämpfung (Martine Jotterand Bellomo). The CBFB sequences presented in this report have been deposited in GenBank (accession numbers AF084955 – AF084970).

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Authors and Affiliations

  1. Department of Human Genetics, Leiden University, Sylvius Laboratories, Leiden, The Netherlands

    Bert A van der Reijden, Hans G Dauwerse, Rachel H Giles, Shantie Jagmohan-Changur, Hans W Wessels, Geoff C Beverstock, Gert-Jan B van Ommen & Martijn H Breuning

  2. Laboratory of Gene Transfer, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland, USA

    Cisca Wijmenga & P Paul Liu

  3. Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands

    Bep Smit & Anne Hagemeijer

  4. Division Autonome de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    Martine Jotterand-Bellomo, Danielle Martinet & Dominique Mühlematter

  5. Laboratoire d'Hématologie, Institut Paoli-Calmettes, Marseille, France

    Marina Lafage-Pochitaloff & Jean Gabert

  6. Laboratoire Universitaire d'Hématologie, Université de Bordeaux, France

    Josy Reiffers & Chrystèle Bilhou-Nabera

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  1. Bert A van der Reijden
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  8. Hans W Wessels
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  10. Martine Jotterand-Bellomo
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  11. Danielle Martinet
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  16. Chrystèle Bilhou-Nabera
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van der Reijden, B., Dauwerse, H., Giles, R. et al. Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly clustered. Oncogene 18, 543–550 (1999). https://doi.org/10.1038/sj.onc.1202321

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