Figure 3.
Mutational landscape by thymic vs nonthymic involvement. (A) Mutation burden in the exome capture space. Thymic GZL (n = 15) had a greater mutation burden than nonthymic GZL (n = 6). Data were generated using the Cancer Genome Atlas data set.33 (B) Coding mutation count within the 217 target genes. Thymic GZL (n = 31) had more coding mutations compared with nonthymic GZL (n = 18). (C) Pairwise comparison of incidence of mutations within thymic GZL vs nonthymic GZL. The comparison was done using Fisher’s exact test among the most recurrently mutated genes, between thymic and nonthymic cases. The size of the bubble is inversely correlated with the P value. Significant results after FDR correction (q < 0.05) are colored in red. Full analysis and FDR testing are provided in supplemental Table 4. (D) Co-oncoplot of the most recurrently mutated genes and BCL2/BCL6 FISH rearrangement status within thymic and nonthymic GZL. Thymic GZL was characterized by the presence of mutations typically seen in PMBCL/cHL and the absence of TP53/BCL2/BIRC6 or BCL2/BCL6 rearrangements in the majority of the samples. Within nonthymic cases, 6 of 18 cases are characterized by the presence of SOCS1/B2M variants, and 7 of 18 cases are characterized by TP53/BCL2/BIRC6. BCL2 and BCL6 rearrangements tended to be enriched in nonthymic GZL cases with TP53/BCL2 mutations. BA, break-apart; GAIN_AMP, gain or amplification; NEG, no FISH abnormality.