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Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia

Oncogene volume 29, pages 2509–2516 (2010)Cite this article

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Abstract

A crucial role of segmental duplications (SDs) of the human genome has been shown in chromosomal rearrangements associated with several genomic disorders. Limited knowledge is yet available on the molecular processes resulting in chromosomal rearrangements in tumors. The t(9;22)(q34;q11) rearrangement causing the 5′BCR/3′ABL gene formation has been detected in more than 90% of cases with chronic myeloid leukemia (CML). In 10–18% of patients with CML, genomic deletions were detected on der(9) chromosome next to translocation breakpoints. The molecular mechanism triggering the t(9;22) and deletions on der(9) is still speculative. Here we report a molecular cytogenetic analysis of a large series of patients with CML with der(9) deletions, revealing an evident breakpoint clustering in two regions located proximally to ABL and distally to BCR, containing an interchromosomal duplication block (SD_9/22). The deletions breakpoints distribution appeared to be strictly related to the distance from the SD_9/22. Moreover, bioinformatic analyses of the regions surrounding the SD_9/22 revealed a high Alu frequency and a poor gene density, reflecting genomic instability and susceptibility to rearrangements. On the basis of our results, we propose a three-step model for t(9;22) formation consisting of alignment of chromosomes 9 and 22 mediated by SD_9/22, spontaneous chromosome breakages and misjoining of DNA broken ends.

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Acknowledgements

We thank Ms MVC Pragnell for language revision of the paper. The financial support of Associazione Italiana contro le Leucemie (AIL)-BARI is gratefully acknowledged.

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Author notes

  1. F Albano, L Anelli and A Zagaria: These authors contributed equally to this work.

  2. M Rocchi and G Specchia: These senior authors equally oversaw the design and conduction of the research.

Authors and Affiliations

  1. Department of Hematology, University of Bari, Bari, Italy

    F Albano, L Anelli, A Zagaria, N Coccaro, V Liso & G Specchia

  2. Department of Genetics and Microbiology, University of Bari, Bari, Italy

    P D'Addabbo & M Rocchi

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  1. F Albano
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  2. L Anelli
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  3. A Zagaria
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  4. N Coccaro
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  5. P D'Addabbo
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  6. V Liso
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  7. M Rocchi
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  8. G Specchia
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Correspondence to F Albano.

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Albano, F., Anelli, L., Zagaria, A. et al. Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia. Oncogene 29, 2509–2516 (2010). https://doi.org/10.1038/onc.2009.524

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