The definition of copy number (CN) clusters using hierarchical clustering and their association with cytogenetic subgroups and significantly mutated genes. (A) CN data derived from 1074 whole-exome sequencing samples identify recurrent regions of gain and loss across the genome. (B) Hierarchical K-means clustering analysis of recurrent CN abnormalities identifies 9 CN clusters, of which 7 were predominantly translocation groups and 2 were hyperdiploid; additional details are listed in the supplemental methods. CN cluster 1 (13.7%) was hyperdiploid and associated with gains of 1q and 6p and expression of CCND2. CN cluster 2 (32.9%) was hyperdiploid with gain of 11q and expression of CCND1, but inversely associated with gain of 1q. CN cluster 3 (5.6%) was associated with t(14;16), deletions of 1p, 8p, 13q, 14q, and 16q, and gain of 1q. CN cluster 4 (5.2%) was associated with t(4;14), del13q, and del14q. CN cluster 5 (6.7%) was associated with t(4;14), del4p, del13q, and del14q as well mutations of NFKBIA, MAX, and TRAF3. CN cluster 6 (5.9%) was associated with deletions of 8p, 14q, and 16q, gain of 1q, and mutation of CYLD. CN cluster 7 (7.9%) was associated with t(4;14) and t(14;16), the APOBEC signature, deletions of 11q and 13q, gain of 1q, and mutation of DIS3. CN cluster 8 (17.3%) was associated with t(11;14) and mutations of CCND1 and PRKD2, but not with any deletions or gains. CN cluster 9 (4.8%) was associated with t(11;14) and gain of 11q as well as mutation of BRAF. The data plotted in this figure are listed in supplemental Table 11. (C) The associations of genetic markers with CN clusters illustrating significant associations and their directionality by the size of the circle; red, positive association; blue, negative association. (D) Progression-free survival Kaplan-Meier plots indicating differences in outcome between CN cluster 7 compared with clusters 1, 2, and 5.