The LMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion.
The Epstein-Barr virus (EBV) is tightly linked to the induction of undifferentiated nasopharyngeal carcinoma (NPC), a tumour endemic in certain areas of southeast Asia. The LMP1 gene encoded by EBV is a classical oncogene due to its ability to transform rodent fibroblasts. LMP1 is absolutely essential for transformation of B cells by the virus and is one of the few EBV genes found to be expressed in NPC. It was originally shown that the LMP1 gene from NPC harbours a deletion of 30 bp in the 3' part of the gene. However, this deletion is also present in the virus spread in healthy people of the areas endemic for NPC and also in other EBV-positive tumours as well as in healthy carriers. We isolated and sequenced the LMP1 gene obtained from tissue of 7 Russian patients with NPC and 1 German patient with an NPC-like tumour of the parotid gland (PG) and compared them with the LMP1 gene isolated from peripheral blood lymphocytes (PBLs) of 6 Russian and 4 German healthy EBV-positive carriers. Neither the Russian NPC cases nor the German NPC-like tumour harboured an LMP1 gene with the 30-bp deletion, while 1 Russian and 2 German carriers contained the LMP1 gene with the 30-bp deletion. In addition, the LMP1 gene isolated from PBLs of the German patient was virtually identical to the gene isolated from the primary tumour. Functional analysis showed no correlation between the presence or absence of the 30-bp deletion and the level of induction of the transcription factors NFkappaB and jun/AP-1 caused by LMP1. These data indicate that the 30-bp deletion is not a factor predisposing for NPC. Comparison of the DNA sequences revealed that the LMP1 genes present in the NPCs most likely represent the "strain" persisting in the general population.
Hahn
P
P
Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie, Gebäude 47, Universitätskliniken, Homburg/Saar, Germany.
Novikova
E
E
Scherback
L
L
Janik
C
C
Pavlish
O
O
Arkhipov
V
V
Nicholls
J
J
Müller-Lantzsch
N
N
Gurtsevitch
V
V
Grässer
F A
FA
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000821:virology*; D010307:Parotid Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000821:virology*; D016133:Polymerase Chain Reaction; D012426:Russia / Q000453:epidemiology; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000302:isolation & purification
D017931:DNA Primers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D008156:Luciferases; D000469:Alkaline Phosphatase