Identification and Characterization of EBV Genome in NKT Cell Lymphoma

Background: Epstein-Barr virus (EBV) is closely related to (Natural Killer/T) NKT cell lymphoma. However, the genomic characteristics of EBV genome in NKT cell lymphoma are poorly understood.

Methods: We targeted the EBV gene sequence of 5 samples of NKT cell lymphoma tissue and identified the genomic variation of EBV in NKT cell lymphoma, and compared with other EBV strains by bioinformatics.

Results: The EBV genome was successfully retrieved from 5 samples and the variation was detected. We found a total of 3220 mutations in 5 cases of NKT cell lymphoma, including 2996 substitutions, 105 insertion and 119 deletion, of which 2103 of the mutations in the gene coding region, others were in the non-coding region. The non-synonymous mutations in 5 samples were 563, 586, 596, 667 and 578, respectively. Most of them were located in the exons of tegument, membrane glycoprotein, transcription factor and replication. Phylogenetic analysis of LMP1, EBNA1, EBNA2, EBNA3A, BZLF1, BLLF1 were performed with other EBV strains. The results showed that the LMP1 and BZLF1 genes of EBV in NKT cell lymphoma were different from those of other EBV strains, suggesting that LMP1 and BZLF1 were specific in NKT cell lymphoma. The comparison of EBNA2 and EBNA3A between EBV in NKT cell lymphoma and other strains suggested that the EBV in NKT cell lymphoma was type I EBV. The characteristics of EBNA1 in different strains have no correlation and need further investigation.

Conclusion: By targeting sequencing technology, we had shown that there were many variations of EBV in NKT cell lymphoma, including substitutions, insertions and deletions, and most of the variations were located in the gene coding region. The EBV in NKT cell lymphoma was type I EBV. LMP1 and BZLF1 in the EBV genome of NKT cell lymphoma were tumor specific and might serve as potential biomarkers for EBV genotyping.