Genomic findings of EBV⁺ nPTCL. (A) The mutational landscape of EBV⁺ nPTCL. The rows contain clinical information, somatic mutation data, and EBV genome deletions. Del, deletions; Amp, amplifications. (B) The distribution of somatic mutations. (C) Presence of TET2 and DNMT3A mutations in the BM or spleen. The identical TET2 mutation was identified in the BM that histopathologically carried no tumor cells in UPN82. TET2 mutations were not obvious in the BM in UPN232. Both TET2 and DNMT3A mutations were identified in the BM in UPN242. The TET2 mutation was present both in the tumor and the spleen in UPN857, whereas the mutation in the tumor was a subject of loss of heterozygosity. (D) Kaplan-Meier plot of the OS of patients with EBV⁺ nPTCL stratified by TET2 (T) and DNMT3A (D) mutations at diagnosis (n = 21). P = .004 by log-rank test. The median OS of patients with DNMT3A mutations, patients with TET2 but without DNMT3A mutations, and patients without TET2 mutations were 0.2, 2.0, and 9 months, respectively. (E) Summary of intragenic deletions identified in EBV genomes of patients with EBV⁺ nPTCL. Each gray bar indicates an EBV genome from a patient with EBV⁺ nPTCL. Blue regions indicate deletions. An orange region indicates an inverted region of an EBV genome. The locations of EBV genome components are also indicated. oriP, replication origin used in latent infection; oriLyt, replication origin used in lytic infection. (F) A complex SV involving both EBV and human genomes identified in UPN312. The patient’s EBV genome incorporated 4 different parts of chromosome 9. Two adjacent pieces of the chromosome encoded DOCK8 and PD-L1, thereby forming DOCK8/PD-L1 fusion. All coding PD-L1 sequences were retained with an initial exon of DOCK8 on the 5′ side, indicating that messenger RNA transcription is driven by the DOCK8 promoter. A large part of the 3′ untranslated region (UTR) of PD-L1 was deleted, which upregulates PD-L1 expression.