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
Pihan, German A.
Kershaw, Glenn R.
Kittler, Ellen L. W.
Quesenberry, Peter J.
Woda, Bruce A.
KeywordsAmino Acid Sequence
Cell Transformation, Neoplastic
Cell Transformation, Viral
Gene Expression Regulation, Viral
Herpesvirus 4, Human
Molecular Sequence Data
Protein Structure, Tertiary
Tumor Virus Infections
Viral Matrix Proteins
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AbstractThis 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.
SourceBlood. 1996 Feb 1;87(3):876-81.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40130
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