ALCLs with DUSP22 rearrangements belong to a unique cluster of ALCLs. (A) Unsupervised hierarchical clustering of gene expression data from 31 frozen ALCL samples shows that DUSP22-rearranged ALCLs segregate independently from ALK-positive ALCLs and are entirely contained within 1 of 2 main clusters (cluster 1). Genes shown were selected on the basis of coefficient of variation of at least 50% and expression in at least 4 samples across the entire data set, agnostic to subtype or cluster. P values reflect the probability that cases of similar type cluster together (Fisher exact test). WHO, WHO subtype. Primary cutaneous (Prim.Cut.) ALCLs did not cluster together significantly (P = .29). (B) Cluster 1 containing all DUSP22-rearranged ALCLs shows depletion of IL-6-JAK-STAT3-associated genes. (C) ALCLs in cluster 1 with low STAT3 gene expression also show low total STAT3 protein and low pSTAT3^Y705 by reverse phase protein array. Genetic subtypes (ALK, DUSP22, or other ALK-negative) are indicated. The 3 cases indicated with DUSP22 rearrangements were systemic ALK-negative ALCLs and correspond to cases 1, 10, and 29 in supplemental Table 2.