A deletion mutant of the LMP1 oncogene of Epstein-Barr virus is associated with evolution of angioimmunoblastic lymphadenopathy into B immunoblastic lymphoma

Details

Serval ID
serval:BIB_B5B2C7A95BAD
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
A deletion mutant of the LMP1 oncogene of Epstein-Barr virus is associated with evolution of angioimmunoblastic lymphadenopathy into B immunoblastic lymphoma
Journal
Leukemia
Author(s)
Knecht  H., Martius  F., Bachmann  E., Hoffman  T., Zimmermann  D. R., Rothenberger  S., Sandvej  K., Wegmann  W., Hurwitz  N., Odermatt  B. F., Kummer  H., Pallesen  G.
ISSN
0887-6924 (Print)
Publication state
Published
Issued date
03/1995
Volume
9
Number
3
Pages
458-65
Notes
Case Reports Journal Article Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV). It is expressed in Reed-Sternberg cells of Hodgkin's disease (HD), tumor cells of nasopharyngeal carcinoma (NPC), and immunoblasts of angioimmunoblastic lymphadenopathy (AILD). A particular LMP1 deletion mutant was recently identified in NPC and clinically and histologically aggressive HD. We studied two patients with AILD that subsequently progressed into immunoblastic lymphoma (IBL) in order to investigate whether the LMP1 deletion mutant was implicated in progression of AILD into IBL. Immunohistology and in situ hybridization were performed on diagnostic biopsies. DNA extracted from fresh frozen material was used for rearrangement studies and polymerase chain reaction (PCR) based amplification and sequencing of portions of the LMP1 gene. Immunohistochemistry revealed B cell origin of both cases of IBL. In the first patient clonal rearrangement of the immunoglobulin heavy-chain gene was present in IBL but not in AILD. In this patient, scattered immunoblasts of AILD and numerous tumor cells of B-IBL were shown to contain EBV transcripts (EBER1) and to express LMP1. Sequence analysis of the LMP1 gene from AILD and IBL in the first, and from IBL in the second patient, revealed identical deletions and point mutations. This LMP1 deletion mutant is identical to those which have been reported in HD and NPC. Its association with evolution of AILD into B-IBL, aggressive HD and NPC, suggests that this particular mutant is more widespread than originally thought and is clinically relevant.
Keywords
Adult Amino Acid Sequence Antigens, Viral/*genetics Base Sequence DNA Mutational Analysis DNA, Neoplasm/genetics DNA, Viral/genetics Disease Progression Fatal Outcome Gene Rearrangement, B-Lymphocyte, Heavy Chain *Genes, Viral *Herpesviridae Infections/virology Herpesvirus 4, Human/classification/*genetics/pathogenicity Humans Immunoblastic Lymphadenopathy/*pathology/virology In Situ Hybridization Lymphoma, B-Cell/*pathology/virology Lymphoma, Lymphoblastic/*pathology/virology Male Middle Aged Molecular Sequence Data *Oncogenes *Point Mutation Polymerase Chain Reaction Reed-Sternberg Cells/virology *Sequence Deletion *Tumor Virus Infections/virology Viral Matrix Proteins/*genetics Viral Structural Proteins/*genetics
Pubmed
Web of science
Create date
25/01/2008 14:36
Last modification date
20/08/2019 15:24
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