To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression.
%0 Journal Article
%1 Sellmann.2010
%A Sellmann, Ludger
%A Scholtysik, Rene
%A Kreuz, Markus
%A Cyrull, Sandra
%A Tiacci, Enrico
%A Stanelle, Jens
%A Carpinteiro, Alexander
%A Nückel, Holger
%A Boes, Tanja
%A Gesk, Stefan
%A Siebert, Reiner
%A Klein-Hitpass, Ludger
%A Dührsen, Ulrich
%A Dürig, Jan
%A Küppers, Ralf
%D 2010
%J Cancer genetics and cytogenetics
%K Ataxia_Telangiectasia_Mutated_Proteins Cell_Cycle_Proteins/genetics Chromosome_Mapping DEAD-box_RNA_Helicases/genetics DNA-Binding_Proteins/genetics Gene_Dosage Gene_Expression_Regulation Gene_Expression_Regulation,_Leukemic Humans In_Situ_Hybridization,_Fluorescence Leukemia,_Lymphocytic,_Chronic,_B-Cell/genetics MicroRNAs/metabolism Polymorphism,_Single_Nucleotide Protein-Serine-Threonine_Kinases/genetics Proto-Oncogene_Proteins_c-bcl-2/genetics Reverse_Transcriptase_Polymerase_Chain_Reaction Tumor_Suppressor_Proteins/genetics Uniparental_Disomy/genetics Up-Regulation
%N 2
%P 149–160
%T Gene dosage effects in chronic lymphocytic leukemia
%V 203
%X To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression.
@article{Sellmann.2010,
abstract = {To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression.},
added-at = {2014-10-14T15:28:12.000+0200},
author = {Sellmann, Ludger and Scholtysik, Rene and Kreuz, Markus and Cyrull, Sandra and Tiacci, Enrico and Stanelle, Jens and Carpinteiro, Alexander and Nückel, Holger and Boes, Tanja and Gesk, Stefan and Siebert, Reiner and Klein-Hitpass, Ludger and Dührsen, Ulrich and Dürig, Jan and Küppers, Ralf},
biburl = {https://www.bibsonomy.org/bibtex/27ebbbe109754bce8a4ac9ea3e73e3abd/drtester},
interhash = {3ff3fea7206d2143bc5ad096518317c2},
intrahash = {7ebbbe109754bce8a4ac9ea3e73e3abd},
journal = {Cancer genetics and cytogenetics},
keywords = {Ataxia_Telangiectasia_Mutated_Proteins Cell_Cycle_Proteins/genetics Chromosome_Mapping DEAD-box_RNA_Helicases/genetics DNA-Binding_Proteins/genetics Gene_Dosage Gene_Expression_Regulation Gene_Expression_Regulation,_Leukemic Humans In_Situ_Hybridization,_Fluorescence Leukemia,_Lymphocytic,_Chronic,_B-Cell/genetics MicroRNAs/metabolism Polymorphism,_Single_Nucleotide Protein-Serine-Threonine_Kinases/genetics Proto-Oncogene_Proteins_c-bcl-2/genetics Reverse_Transcriptase_Polymerase_Chain_Reaction Tumor_Suppressor_Proteins/genetics Uniparental_Disomy/genetics Up-Regulation},
number = 2,
pages = {149–160},
timestamp = {2014-10-14T15:28:12.000+0200},
title = {Gene dosage effects in chronic lymphocytic leukemia},
volume = 203,
year = 2010
}