title: Clonal deleted latent membrane protein 1 variants of Epstein-Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment.
abstract: Extranodal natural killer/T-cell lymphomas (NK/TL), rare in Europe, are Epstein-Barr virus (EBV) associated lymphomas with poor outcomes. Here, we determined the virus type and analyzed the EBV latent membrane protein-1 (LMP1) gene sequence in NK/TL from French patients. Six clones of viral LMP1 were sequenced by Sanger technology in blood from 13 patients before treatment with an l-asparaginase based regimen and, for 8 of them, throughout the treatment. Blood LMP1 sequences from 21 patients without any known malignancy were tested as controls. EBV Type A was identified for 11/13 patients and for all controls. Before treatment, a clonal LMP1 gene containing a 30 bp deletion (del30) was found in 46.1% of NK/TL and only in 4.8% of controls. Treatment was less effective in these patients who died more rapidly than the others. Patients with a deleted strain evolving toward a wild-type strain during treatment reached complete remission. The LMP1 gene was sequenced by highly sensitive next-generation sequencing technology in five NK/TL nasopharyngeal biopsies, two of them originating from the previous patients. Del30 was present in 100% of the biopsies; two viruses at least coexisted in three biopsies. These results suggest that del30 may be associated with poor prognosis NK/TL and that strain evolution could be used as a potential marker to monitor treatment.
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Limoges, France.
authors.forename: Mohamad Adnan
authors.initials: MA
authors.lastname: Halabi
authors.affiliation: Department of Clinical Hematology, University Hospital Dupuytren, Limoges, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: Department of Génolim, University, Limoges, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Moulinas
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Limoges, France.
authors.forename: Racha
authors.initials: R
authors.lastname: Bahri
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Limoges, France.
authors.forename: Hazar
authors.initials: H
authors.lastname: Al Mouhammad
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Limoges, France.
authors.forename: Nour
authors.initials: N
authors.lastname: Mammari
authors.affiliation: Department of Biological Hematology, University Hospital Dupuytren, Limoges, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Limoges, France.|Department of Virology, University Hospital Dupuytren, CBRS, Limoges, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ranger-Rogez
mesh_terms: D000328:Adult; D000368:Aged; D002461:Cell Line, Transformed; D060965:Clonal Evolution; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005060:Europe; D005260:Female; D017353:Gene Deletion; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000209:etiology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014763:Viral Matrix Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins
keywords: EBV; LMP-1; NGS; NK/T lymphoma; l-asparaginase