Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect

  • Authors:
    • John D. Dickinson
    • Avadhut Joshi
    • Javeed Iqbal
    • Warren Sanger
    • Philip J. Bierman
    • Shantaram S. Joshi
  • View Affiliations

  • Published online on: May 1, 2006     https://doi.org/10.3892/ijmm.17.5.769
  • Pages: 769-778
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Abstract

This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.

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May 2006
Volume 17 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Dickinson JD, Joshi A, Iqbal J, Sanger W, Bierman PJ and Joshi SS: Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect. Int J Mol Med 17: 769-778, 2006
APA
Dickinson, J.D., Joshi, A., Iqbal, J., Sanger, W., Bierman, P.J., & Joshi, S.S. (2006). Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect. International Journal of Molecular Medicine, 17, 769-778. https://doi.org/10.3892/ijmm.17.5.769
MLA
Dickinson, J. D., Joshi, A., Iqbal, J., Sanger, W., Bierman, P. J., Joshi, S. S."Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect". International Journal of Molecular Medicine 17.5 (2006): 769-778.
Chicago
Dickinson, J. D., Joshi, A., Iqbal, J., Sanger, W., Bierman, P. J., Joshi, S. S."Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect". International Journal of Molecular Medicine 17, no. 5 (2006): 769-778. https://doi.org/10.3892/ijmm.17.5.769