Genetics and genomics of extranodal natural killer/T cell lymphoma: from etiology to treatment

and of extranodal natural killer/T cell lymphoma: from etiology to treatment. J Transl Abstract Extranodal natural killer/T cell lymphoma (NKTCL) is a heterogenous and unique epidemiological non-Hodgkin’s lymphoma, which is strongly associated with Epstein-Barr virus (EBV) infection. Based on the development of various sequencing methods and molecular biology technologies, genome- and transcriptome-wide association studies of NKTCL have provided insight into the etiology and pathogenesis of NKTCL. Comparative genomic hybridization detected variations in tumor suppressor genes such as PRDM1 , RUNX3 , and EZH2 . Whole-exome sequencing identified pathogenic variant such as DDX3X , and TP53 . Signal pathways such as the Janus kinase/signal transduction and activator of transcription pathway and nuclear factor kappaB pathway are frequently abnormal in NKTCL. In addition, programmed death-1, programmed death ligand-1, and the human leukocyte antigen risk alleles are significantly associated with NKTCL pathogenesis. Meanwhile, epigenetics analysis has also exposited changes such as PTPRK , HACE1 , microRNAs, and long non-coding RNAs, which play important role on the development and biology of NKTCL. EBV infection is tightly correlated with NKTCL. Viral genomic alterations and lytic genes of EBV are reported to have pathogenic effects on host cells that contribute to the etiology of NKTCL. We summarize the genomic and genetic alterations during the pathogenesis and development of NKTCL and exhibit the potential therapeutic targets that are worth exploring in future research and clinical trials. (2/7) [98] Sanger sequencing revealed that LMP1 gene contained a 30 bp deletion, which may be related to the poor prognosis of NKTCL patients [99] . Analyzing the EBV genome and transcriptome derived from NKTCL, in addition to the 30 bp deletion in LMP1 , small deletions in BARTs , EBNA2 , EBNA3s , BLLF1/2 , and other regions were also detected, which disclosed the heterogeneity in EBV cloning in NKTCL patients [17] . Interestingly, this study also clarified an insertion of EBV fragments into the human nonhomologous end-joining 1 ( NHEJ1 ) gene region, which may lead to changes in the expression and function of NHEJ1 . The NHEJ1 gene is vital in repairing DNA damage and maintaining genome stability [100] . Thus, integration of the EBV genome and human genome might have crucial impact on the pathogenesis and development of NKTCL. The molecular mechanism of this integration affecting NKTCL tumorigenesis and whether indeed contributes to clinical treatment of NKTCL need