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

Dickinson,John D.; Joshi,Avadhut; Iqbal,Javeed; Sanger,Warren; Bierman,Philip J.; Joshi,Shantaram S.

doi:10.3892/ijmm.17.5.769

May 2006 Volume 17 Issue 5

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May 2006 Volume 17 Issue 5

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Article

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 / Copyright

Affiliations: Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-6395, USA
Pages: 769-778
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Published online on: May 1, 2006

https://doi.org/10.3892/ijmm.17.5.769
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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.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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