title: Latent membrane protein 1 deletion mutants accumulate in reed-sternberg cells of human immunodeficiency virus-related Hodgkin's lymphoma.
abstract: The origin and biological significance of deletions at the 3' end of the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) gene are still controversial. We herein demonstrate that LMP-1 deletion mutants are highly associated with human immunodeficiency virus-related Hodgkin's lymphoma (HIV-HL) of Italian patients (29 of 31 cases; 93.5%), a phenomenon that is not due to a peculiar distribution of EBV strains in this area. In fact, although HIV-HL patients are infected by multiple EBV variants, we demonstrate that LMP-1 deletion mutants preferentially accumulate within neoplastic tissues. Subcloning and sequencing of the 3' LMP-1 ends of two HIV-HL genes in which both variants were present showed the presence of molecular signatures suggestive of a likely derivation of the LMP-1 deletion mutant from a nondeletion ancestor. This phenomenon likely occurs within tumor cells in vivo, as shown by the detection of both LMP-1 variants in single microdissected Reed-Sternberg cells, and may at least in part explain the high prevalence of LMP-1 deletions associated with HIV-HL.
authors.affiliation: Immunovirology and Biotherapy Unit, Department of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, via Pedemontana Occidentale 12, 33081 Aviano (PN) Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Guidoboni
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Laura
authors.initials: L
authors.lastname: Caggiari
authors.forename: Antonia A
authors.initials: AA
authors.lastname: Lettini
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Valli
authors.initials: V
authors.lastname: De Re
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.forename: Paola
authors.initials: P
authors.lastname: Zancai
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Mauro
authors.initials: M
authors.lastname: Boiocchi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D017353:Gene Deletion; D006566:Herpesviridae Infections / Q000453:epidemiology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D016483:Lymphoma, AIDS-Related / Q000473:pathology*; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000821:virology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human