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M9650277.TXT
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1996-03-09
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Document 0277
DOCN M9650277
TI Deletion variants within the NF-kappa B activation domain of the LMP1
oncogene prevail in acquired immunodeficiency syndrome-related large
cell lymphomas and human immunodeficiency virus-negative atypical
lymphoproliferations.
DT 9605
AU Knecht H; Raphael M; McQuain C; Rothenberger S; Pihan G; Camilleri-Broet
S; Bachmann E; Kershaw GR; Ryan S; Kittler EL; Quesenberry PJ; Schlaifer
D; Woda BA; Brousset P; LINK Laboratories, University of Massachusetts
Medical Center,; Worcester 01655-0246, USA.
SO Blood. 1996 Feb 1;87(3):876-81. Unique Identifier : AIDSLINE
MED/96151965
AB This sequencing study of 17 acquired immunodeficiency syndrome-related
lymphomas (9 primary brain, 8 systemic) and 8 human immunodeficiency
virus-negative atypical lymphoproliferations expressing large amounts of
the latent membrane protein 1 (LMP1) of Epstein-Barr virus was performed
to characterize the carboxy terminal NF-kappa B activation domain of
LMP1 at the molecular level in an immunocompromised host. In-frame
deletions within the NF-kappa B activation domain were identified in all
but 2 primary brain lymphomas, 4 systemic lymphomas, and 4 atypical
lymphoproliferations, ie, in 60% of cases. In addition, non silent point
mutations (range 1 to 5, mean 3.3) were detected in all cases. Although
all changes occurred within the first 100 nucleotides of the carboxy
terminal NF-kappa B activation domain--a critical sequence for the
protein half-life--not a single point mutation was found in the
remaining 62 nucleotides, necessary for malignant transformation. Such a
clustering of nonrandom sequence variations, associated with a high
oncoprotein expression in immunocompromised hosts, suggests that this
part of the LMP1 oncogene behaves as a hypervariable region with natural
selection of growth-promoting variants through prolongation of the
protein half-life.
DE Amino Acid Sequence Base Sequence Brain Neoplasms/GENETICS/VIROLOGY
Cell Transformation, Neoplastic/*GENETICS Cell Transformation,
Viral/*GENETICS Gene Expression Regulation, Viral Half-Life
Herpesviridae Infections/*VIROLOGY Herpesvirus 4,
Human/*GENETICS/ISOLATION & PURIF/PHYSIOLOGY Human HIV Seronegativity
Lymphoma, AIDS-Related/GENETICS/*VIROLOGY Lymphoproliferative
Disorders/GENETICS/*VIROLOGY Molecular Sequence Data NF-kappa
B/*METABOLISM Point Mutation Protein Structure, Tertiary Selection
(Genetics) Sequence Alignment Sequence Deletion Support, Non-U.S.
Gov't Tumor Virus Infections/*VIROLOGY Viral Matrix
Proteins/CHEMISTRY/*GENETICS/METABOLISM JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).