Fig. 3

ENKTL harbors frequent PD-L1 SVs, leading to its overexpression. a FISH analysis showing PD-L1 break-apart (middle) and cluster formation (right) in ENKTL cells. Design of the break-apart assay using BAC probes recognizing the 5′-part (green) and 3′-part (red) of PD-L1 loci is shown. Amp, amplification. b PD-L1 IHC (top and middle) and EBER-ISH (bottom) of ENKTL cases with or without PD-L1 genetic alterations. Antibodies specifically detecting N-terminal (top) and C-terminal (middle) domains of PD-L1 were used. c Percentage of Ki-67+ cells in tumor cell fraction in ENKTL cases with or without PD-L1 genetic alterations. Each dot represents a single case. **P < 0.005, Brunner–Munzel test. A summary of the results is shown in Table 1. d Frequently altered genes identified by whole-exome sequencing for 25 ENKTL cases [28]. Type of somatic alterations is indicated by color. e Hierarchy of somatic mutations and PD-L1 SVs is shown with their allele frequencies in 8 ENKTL cases analyzed by whole-exome sequencing. Driver mutations are shown in green, and PD-L1 SVs are shown in red