High frequency of Epstein Barr virus latent membrane protein-1 30 bp deletion in a series of pediatric malignancies in Argentina.
Epstein Barr virus widely infects human populations and remains mostly asymptomatic; however, it has been associated with several malignancies. The EBV-encoded latent membrane protein-1 has been involved in neoplasic transformation; a 30-bp deletion and several mutations in the COOH-terminal domain have been associated with histopathological and clinical disease features.


OBJECTIVE
To analyze and correlate the presence of mutations and a 30-bp deletion with the influence of LMP-1 on tumorigenicity in a population of EBV+ pediatric malignancies.


METHODS
We studied EBV presence by LMP-1 immunohistochemistry, EBERs in situ hybridization and PCR in fresh and formalin-fixed paraffin-embedded tissue samples from 10 Hodgkin's lymphomas, 6 non-Hodgkin's lymphomas, 4 undifferentiated nasopharyngeal carcinomas. Eighteen out of 20 samples were sequenced. Eight fresh normal lymphoid tissue samples and 3 peripheral blood samples were analyzed.


RESULTS
All cases were EBV positive. EBV typing rendered 12 EBV-1 and 8 EBV-2. Del-LMP-1 was detected in 15/20 EBV related malignancies, as well as in 4/11 control tissues. A high percentage of patients showed point mutations previously described. The presence of del-LMP-1 and point mutations failed to correlate with clinical course.


CONCLUSIONS
We found a marked incidence of del-LMP-1 (75%) in our series. However, we failed to find any correlation between histological aggressiveness of malignancies and the presence of del-LMP-1 and point mutations.
Chabay
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P
Virology Laboratory, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina. paola_chabay2@yahoo.com.ar
De Matteo
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E
Merediz
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Preciado
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MV
D000293:Adolescent; D001118:Argentina; D001483:Base Sequence; D002277:Carcinoma / Q000473:pathology / Q000821:virology*; D002648:Child; D004279:DNA, Viral / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity; D006689:Hodgkin Disease / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D014763:Viral Matrix Proteins / Q000032:analysis / Q000235:genetics*; D017735:Virus Latency
D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D014763:Viral Matrix Proteins