title: Genomic loss of the putative tumor suppressor gene E2A in human lymphoma.
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.
authors.affiliation: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Steininger
authors.forename: Markus
authors.initials: M
authors.lastname: Möbs
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Karl
authors.initials: K
authors.lastname: Köchert
authors.forename: Stephan
authors.initials: S
authors.lastname: Kreher
authors.forename: Björn
authors.initials: B
authors.lastname: Lamprecht
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.forename: Martin
authors.initials: M
authors.lastname: Janz
authors.forename: Claus-Detlev
authors.initials: CD
authors.lastname: Klemke
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Evelin
authors.initials: E
authors.lastname: Schrock
authors.forename: Stephan
authors.initials: S
authors.lastname: Mathas
authors.forename: Chalid
authors.initials: C
authors.lastname: Assaf
mesh_terms: D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency* / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D055028:Comparative Genomic Hybridization; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007963:Leukocytes, Mononuclear; D008969:Molecular Sequence Data; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012751:Sezary Syndrome / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051361:Cyclin-Dependent Kinase 6; D017931:DNA Primers; D016271:Proto-Oncogene Proteins c-myc; D018631:ras Proteins; C489427:MYC protein, human; C407909:TCF3 protein, human; C495911:CDK6 protein, human