title: 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.
abstract: 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.
authors.affiliation: LINK Laboratories, University of Massachusetts Medical Center, Worcester 01655-0246, USA.
authors.forename: H
authors.initials: H
authors.lastname: Knecht
authors.forename: M
authors.initials: M
authors.lastname: Raphaël
authors.forename: C
authors.initials: C
authors.lastname: McQuain
authors.forename: S
authors.initials: S
authors.lastname: Rothenberger
authors.forename: G
authors.initials: G
authors.lastname: Pihan
authors.forename: S
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: E
authors.initials: E
authors.lastname: Bachmann
authors.forename: G R
authors.initials: GR
authors.lastname: Kershaw
authors.forename: S
authors.initials: S
authors.lastname: Ryan
authors.forename: E L
authors.initials: EL
authors.lastname: Kittler
authors.forename: P J
authors.initials: PJ
authors.lastname: Quesenberry
authors.forename: D
authors.initials: D
authors.lastname: Schlaifer
authors.forename: B A
authors.initials: BA
authors.lastname: Woda
authors.forename: P
authors.initials: P
authors.lastname: Brousset
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D018023:HIV Seronegativity; D006207:Half-Life; D006566:Herpesviridae Infections / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000821:virology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012641:Selection, Genetic; D016415:Sequence Alignment; D017384:Sequence Deletion; D014412:Tumor Virus Infections / Q000821:virology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins