DELETION VARIANTS WITHIN THE NF-KAPPA-B ACTIVATION DOMAIN OF THE LMP1ONCOGENE PREVAIL IN ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED LARGE-CELL LYMPHOMAS AND HUMAN IMMUNODEFICIENCY VIRUS-NEGATIVE ATYPICAL LYMPHOPROLIFERATIONS
H. Knecht et al., DELETION VARIANTS WITHIN THE NF-KAPPA-B ACTIVATION DOMAIN OF THE LMP1ONCOGENE PREVAIL IN ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED LARGE-CELL LYMPHOMAS AND HUMAN IMMUNODEFICIENCY VIRUS-NEGATIVE ATYPICAL LYMPHOPROLIFERATIONS, Blood, 87(3), 1996, pp. 876-881
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 perf
ormed to characterize the carboxy terminal NF-kappa B activation domai
n of LMP1 at the molecular level in an immunocompromised host. in-fram
e deletions within the NF-kappa B activation domain were identified in
all but 2 primary brain lymphomas, 4 systemic lymphomas, and 4 atypic
al lymphoproliferations, ie, in 60% of cases. In addition, non silent
point mutations (range 1 to 5, mean 3.3) were detected in all cases. A
lthough all changes occurred within the first 100 nucleotides of the c
arboxy terminal NF-kappa B activation domain-a critical sequence for t
he protein half-life-not a single point mutation was found in the rema
ining 62 nucleotides, necessary for malignant transformation. Such a c
lustering of nonrandom sequence variations, associated with a high onc
oprotein expression in immunocompromised hosts, suggests that this par
t of the LMP1 oncogene behaves as a hypervariable region with natural
selection of growth-promoting variants through prolongation of the pro
tein half-life. (C) 1996 by The American Society of Hematology.