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.
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.
Knecht
H
H
LINK Laboratories, University of Massachusetts Medical Center, Worcester 01655-0246, USA.
Raphaël
M
M
McQuain
C
C
Rothenberger
S
S
Pihan
G
G
Camilleri-Broët
S
S
Bachmann
E
E
Kershaw
G R
GR
Ryan
S
S
Kittler
E L
EL
Quesenberry
P J
PJ
Schlaifer
D
D
Woda
B A
BA
Brousset
P
P
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
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins