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Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations

Oncogene volume 18, pages 6271–6277 (1999)Cite this article

Abstract

The increased or inappropriate expression of genes with oncogenic properties through specific chromosome translocations is an important event in the pathogenesis of B-cell lymphoproliferative diseases. Recent studies have found deletions or translocations of chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21 – q22 region being most frequently affected. In three patients with translocations between chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.

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Acknowledgements

We thank Anton Kruger for patient sample P2, Samantha Johnson, Sharron Glide, Delin Zhu and Mary Tiller for technical assistance; Anne Gardiner for helpful discussions and critical reading of the manuscript. This work was supported by grants from the Leukemia Research Fund UK and the Medical Research Council of Canada (MRC) to SW Scherer and L-CT Sui. SW Scherer is a Scholar and L-CT Sui a Senior Scientist of the MRC and both are members of the Canadian Genetic Diseases Network.

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Authors and Affiliations

  1. Department of Haematology, Royal Bournemouth Hospital, Castle Lane East, Bournemouth, Dorset, BH7 7DW, UK

    M M Corcoran, S J Mould, J A Orchard, R E Ibbotson, R M Chapman & D G Oscier

  2. Department of Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada

    A P Boright, C Platt, L-C Tsui & S W Scherer

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  1. M M Corcoran
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Corcoran, M., Mould, S., Orchard, J. et al. Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations. Oncogene 18, 6271–6277 (1999). https://doi.org/10.1038/sj.onc.1203033

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