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).