Co-occurring genetic alterations in cHL. (A) Genetic alterations are visualized in a color-coded matrix. Mutations and SCNAs with a false discovery rate–corrected q < 0.1 and SVs detected in $≥$2 cases. Left: primary EBV⁺ cases; right: EBV^– cases. Morphologic subtype as labeled. Each column represents an individual cHL sample. Clustering of alterations used the 1-Pearson-correlation method. Right: frequency of the genetic alterations are presented as a bar graph. (B) Genetic alterations identified in primary cHLs in panel A are shown in cHL cell lines. (C) Graphical comparison of the number of driver events in EBV⁺ vs EBV^–, MC vs NSHL, and ARID1A wild-type (WT) vs mutant cHLs. MC cHLs are shown in red. (D) Genetic bases of perturbed MHC class I and MHC class II expression in the cHLs. IGV plot of copy number from chromosome 6p21.32 to 6p21.33 reveals copy loss of MHCII and/or MHCI, including HLA-B, in individual cHLs. The EBV status, B2M and HLA-B mutations, and CIITA SVs in individual cHLs are indicated in the header. *Indicates 9 cHLs for which additional flow cytometry analysis was performed. (E) Table comparing the HRS cell MHC class II expression levels in tumors with known MHCII status (copy loss or no copy loss). The P value (P = .048) was determined by using a Fisher’s exact test (see also supplemental Figure 7). non-syn, non-synonymous.