Genomic loss of the putative tumor suppressor gene E2A in human lymphoma

Autor: Karl Köchert, Stephan Mathas, Michael Hummel, Ioannis Anagnostopoulos, Björn Lamprecht, Claus-Detlev Klemke, Reinhard Ullmann, Evelin Schröck, Harald Stein, Stephan Kreher, Markus Möbs, Chalid Assaf, Wolfram Sterry, Anne Steininger, Julia Richter, Martin Janz, Bernd Dörken, Marc Beyer
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Cancer Research
Tumor suppressor gene
Immunology
Molecular Sequence Data
chemical and pharmacologic phenomena
Electrophoretic Mobility Shift Assay
Cell Line
Proto-Oncogene Proteins c-myc
hemic and lymphatic diseases
medicine
Basic Helix-Loop-Helix Transcription Factors
Immunology and Allergy
T-cell lymphoma
Humans
Sezary Syndrome
Transcription factor
Derepression
In Situ Hybridization
Fluorescence
Cell Proliferation
DNA Primers
Comparative Genomic Hybridization
biology
Base Sequence
Genome
Human
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Cell Cycle
Brief Definitive Report
hemic and immune systems
Cyclin-Dependent Kinase 6
Sequence Analysis
DNA
Cell cycle
medicine.disease
Flow Cytometry
Immunohistochemistry
Lymphoma
Gene expression profiling
Gene Expression Regulation
Neoplastic
Genes
T-Cell Receptor beta
biology.protein
Cancer research
Leukocytes
Mononuclear
ras Proteins
Cyclin-dependent kinase 6
tissues
Gene Deletion
Signal Transduction
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
Popis: Loss of E2A, observed in more than 70% of patients with Sézary syndrome, which is a subtype of T cell lymphoma, results in altered expression of genes potentially relevant to oncogenesis.
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.
Databáze: OpenAIRE
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