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Clonal deleted latent membrane protein 1 variants of Epstein‐Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment
Author(s) -
Halabi Mohamad Adnan,
Jaccard Arnaud,
Moulinas Rémi,
Bahri Racha,
Al Mouhammad Hazar,
Mammari Nour,
Feuillard Jean,
RangerRogez Sylvie
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30128
Subject(s) - virus , epstein–barr virus , virology , biology , malignancy , gene , lymphoma , sanger sequencing , herpesviridae , immunology , viral disease , dna sequencing , genetics
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.