Genomic and Transcriptomic Characterization of Natural Killer T Cell Lymphoma

Cancer Cell. 2020 Mar 16;37(3):403-419.e6. doi: 10.1016/j.ccell.2020.02.005.

Abstract

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

Keywords: Epstein-Barr virus; MYC; RAS; RNA helicase; RNA sequencing; copy number variation; genomics; histone acetylation; natural killer/T cell lymphoma; programmed cell death protein-1.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / mortality
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / virology
  • Molecular Targeted Therapy
  • Mutation
  • Natural Killer T-Cells / pathology
  • Phylogeny
  • Transcriptome
  • Whole Genome Sequencing
  • Xenograft Model Antitumor Assays
  • Zebrafish