Genomic and transcriptomic landscapes of Epstein-Barr virus in extranodal natural killer T-cell lymphoma

Rou Jun Peng, Bo Wei Han, Qing Qing Cai, Xiao Yu Zuo, Tao Xia, Jie Rong Chen, Li Na Feng, Jing Quan Lim, Shu Wei Chen, Mu Sheng Zeng, Yun Miao Guo, Bo Li, Xiao Jun Xia, Yi Xia, Yurike Laurensia, Burton Kuan Hui Chia, Hui Qiang Huang, Ken He Young, Soon Thye Lim, Choon Kiat OngYi Xin Zeng, Jin Xin Bei

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Extranodal natural killer T-cell lymphoma (nasal type; NKTCL) is an aggressive malignancy strongly associated with Epstein-Barr virus (EBV) infection. However, the role of EBV in NKTCL development is unclear, largely due to the lack of information about EBV genome and transcriptome in NKTCL. Here, using high-throughput sequencing, we obtained whole genome (n = 27) and transcriptome datasets (n = 18) of EBV derived from NKTCL tumor biopsies. We assembled 27 EBV genomes and detected an average of 1,152 single nucleotide variants and 44.8 indels (<50 bp) of EBV per sample. We also identified frequent focal EBV genome deletions and integrated EBV fragments in the host genome. Moreover, Phylogenetic analysis revealed that NKTCL-derived EBVs are closely clustered; transcriptome analysis revealed less activation of both latent and lytic genes and larger amount of T-cell epitope alterations in NKTCL, as compared with other EBV-associated cancers. Furthermore, we observed transcriptional defects of the BARTs miRNA by deletion, and the disruption of host NHEJ1 by integrated EBV fragment, implying novel pathogenic mechanisms of EBV. Taken together, we reported for the first time global mutational and transcriptional profiles of EBV in NKTCL clinical samples, revealing important somatic events of EBV and providing insights to better understanding of EBV’s contribution in tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1451-1462
Number of pages12
JournalLeukemia
Volume33
Issue number6
DOIs
StatePublished - Jun 1 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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