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Patterns of genetic alterations in B-NHL
C3, EZB and BCL2 clusters from prior whole exome sequencing studies of DLBCL3,49,50 (Fisher test P-values: P=0.0006, P=0.0148 and P=0.0173, respectively). Two clus- ters (Clusters 2 and 3) were enriched in DLBCL, with lower frequencies of mutations in a larger number of genes, in line with the genetic heterogeneity of this disease.3,4 Cluster 2 includes co-associated genetic alterations that overlapped with the previously described C5, MCD, and MYD88 clus- ters3,4 (Fisher P-values: P=0.0004, P=0.0002 and P=0.0007, respectively) including CD79B, MYD88 and TBL1XR1 mutations. Genes within Cluster 3 overlapped in a statisti- cally significant manner with those in the previously
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described C4 and SOCS1/SGK1 clusters (Fisher P-values: P=0.0002 and P=0.0074, respectively), including SGK1, TET2, SOCS1 and histone H1 genes. We also identified a cluster consisting of TP53 mutations and multiple CNA (Cluster 5) similar to the genetically complex C2/A53 sub- type reported in DLBCL;3,49 however, the overlap of features within these clusters could not be formally assessed due to differing annotations. The CNA captured in this cluster were variably represented across B-NHL subtypes, but were most frequent in DLBCL. B-NHL subtypes therefore harbor characteristic clusters of co-associated genetic alter- ations that likely cooperate in disease etiology.
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