Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia—unexpected expression pattern of the RHO GTPase activator ARHGAP20
Tobias Herold
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorVindi Jurinovic
Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
Search for more papers by this authorMedhanie Mulaw
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorTill Seiler
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorAnnika Dufour
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorStephanie Schneider
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorPurvi M. Kakadia
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorMichaela Feuring-Buske
Comprehensive Cancer Center and Department of Internal Medicine III, Institute of Experimental Cancer Research, University of Ulm, Germany
Search for more papers by this authorJan Braess
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorKarsten Spiekermann
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorUlrich Mansmann
Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
Search for more papers by this authorWolfgang Hiddemann
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorChristian Buske
Comprehensive Cancer Center and Department of Internal Medicine III, Institute of Experimental Cancer Research, University of Ulm, Germany
Search for more papers by this authorCorresponding Author
Stefan K. Bohlander
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Department of Internal Medicine III, University of Munich Hospital Großhadern, Ludwig-Maximilians Universität, Campus Großhadern, Marchioninistr. 15, 81377 München, GermanySearch for more papers by this authorTobias Herold
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorVindi Jurinovic
Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
Search for more papers by this authorMedhanie Mulaw
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorTill Seiler
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorAnnika Dufour
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorStephanie Schneider
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorPurvi M. Kakadia
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorMichaela Feuring-Buske
Comprehensive Cancer Center and Department of Internal Medicine III, Institute of Experimental Cancer Research, University of Ulm, Germany
Search for more papers by this authorJan Braess
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorKarsten Spiekermann
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorUlrich Mansmann
Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
Search for more papers by this authorWolfgang Hiddemann
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Search for more papers by this authorChristian Buske
Comprehensive Cancer Center and Department of Internal Medicine III, Institute of Experimental Cancer Research, University of Ulm, Germany
Search for more papers by this authorCorresponding Author
Stefan K. Bohlander
Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, and Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, Munich, Germany
Department of Internal Medicine III, University of Munich Hospital Großhadern, Ludwig-Maximilians Universität, Campus Großhadern, Marchioninistr. 15, 81377 München, GermanySearch for more papers by this authorAbstract
In chronic lymphocytic leukemia (CLL), 13q14 and 11q22-23 deletions are found in 2/3 of the cases. 11q22-23 deletions are associated with poor survival, whereas 13q14 deletions as single abnormality are often found in indolent disease forms. The molecular basis for this difference in prognosis is not known. We examined the 13q14 and 11q22-23 minimally deleted regions (MDRs) for differentially expressed genes by analyzing 154 microarray CLL gene expression data sets. We were able to generate a detailed gene expression map of the MDRs demonstrating a gene dosage effect. Surprisingly, ARHGAP20 encoding the RHO GTPase activating protein 20, which is located in the 11q22-23 MDR, showed—counterintuitively—a significantly higher expression in cases with 11q22-23 deletions compared with cases with no detectable genetic lesion or trisomy 12. Interestingly, cases with 13q14 deletions also had higher ARHGAP20 expression. These expression level changes were confirmed by quantitative PCR in 110 additional CLL samples. The ARHGAP20 gene encodes an evolutionarily conserved protein. In the zebra fish (Danio rerio) genome the syntenic regions of human chromosomal bands 13q14 and 11q22-23 are juxtaposed. The similar expression profiles of ARHGAP20 in 13q14 and 11q22-23 deleted CLL cases suggest a molecular connection and an intriguing mechanism of regulation. © 2011 Wiley-Liss, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| GCC_20879_sm_Suppfig1.tif4.5 MB | Supporting Figure 1 |
| GCC_20879_sm_Suppfig2.tif3.4 MB | Supporting Figure 2 |
| GCC_20879_sm_Suppfig3.tif3.4 MB | Supporting Figure 3 |
| GCC_20879_sm_Suppinfo.doc259 KB | Supporting Information |
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