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Item Type: | Article |
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Title: | Genomic loss of the putative tumor suppressor gene E2A in human lymphoma |
Creators Name: | Steininger, A., Moebs, M., Ullmann, R., Koechert, K., Kreher, S., Lamprecht, B., Anagnostopoulos, I., Hummel, M., Richter, J., Beyer, M., Janz, M., Klemke, C.D., Stein, H., Doerken, B., Sterry, W., Schrock, E., Mathas, S. and Assaf, C. |
Abstract: | The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity. |
Keywords: | Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Cell Cycle, Cell Line, Cell Proliferation, Comparative Genomic Hybridization, Cyclin-Dependent Kinase 6, DNA Primers, DNA Sequence Analysis, Electrophoretic Mobility Shift Assay, Flow Cytometry, Fluorescence In Situ Hybridization, Gene Deletion, Human Genome, Immunohistochemistry, Mononuclear Leukocytes, Molecular Sequence Data, Neoplastic Gene Expression Profiling, Proto-Oncogene Proteins c-myc, ras Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sezary Syndrome, Signal Transduction, T-Cell Receptor beta Genes |
Source: | Journal of Experimental Medicine |
ISSN: | 0022-1007 |
Publisher: | Rockefeller University Press |
Volume: | 208 |
Number: | 8 |
Page Range: | 1585-1593 |
Date: | 1 August 2011 |
Additional Information: | (c) 2011 Steininger et al. |
Official Publication: | https://doi.org/10.1084/jem.20101785 |
PubMed: | View item in PubMed |
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