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
LINK Laboratories; Cancer Center; Department of Pathology; Molecular Medicine
Amino Acid Sequence; Base Sequence; Brain Neoplasms; Cell Transformation, Neoplastic; Cell Transformation, Viral; Gene Expression Regulation, Viral; HIV Seronegativity; Half-Life; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Lymphoma, AIDS-Related; Lymphoproliferative Disorders; Molecular Sequence Data; NF-kappa B; Point Mutation; Protein Structure, Tertiary; Selection (Genetics); Sequence Alignment; Sequence Deletion; Tumor Virus Infections; Viral Matrix Proteins
Medical Immunology | Oncology | Pathology | Virus Diseases
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.
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Citation: Blood. 1996 Feb 1;87(3):876-81.
Knecht, Hans; Raphael, Martine; McQuain, Cathy; Rothenberger, Sylvia; Pihan, German A.; Camilleri-Broët, Sophie; Bachmann, Edith; Kershaw, Glenn R.; Ryan, Shannon; Kittler, Ellen L. W.; Quesenberry, Peter J.; Schlaifer, Daniel; Woda, Bruce A.; and Brousset, Pierre, "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" (1996). Open Access Articles. 293.