Supplementary Figures from Whole-Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating Driver Mutations in African Men with Treatment-Naïve, High-Risk Prostate Cancer

Supplementary Fig. S1 Transition and transversion rates of somatic SNVs observed among six SAPCS patients. Ti and Tv indicate transitional and transversional changes, respectively. Supplementary Fig. S2 Genomic rearrangements between African and European cohorts. A, Those observed for deletions (DEL), inter-chromosomal translocations (CTX), inversions (INV) and tandem duplications (DUP). B, Those observed for the four following types of large deletions: chromosomal deletions (CD), exon losses (EL), splice acceptor variant (SA), and splice donor variant (SD). Supplementary Fig. S3 Complex genomic rearrangements. A, Circos plots depicting coordinated chained events of chromoplexy in SAPCS (n = 1/6) and APCRCEUR (n = 5/9). Somatic copy number gains (red) and losses (blue) are depicted in the inner ring, while chromoplexic events between chromosomes are linked with blue lines and rearrangements not assigned to a chained event are depicted as gray lines within the plot. B, Maximal chromothriptic scores observed among tumor-matched blood pairs of SAPCS and APCRCEUR cohorts. Tumors with a ShatterProof score over 0.39 are defined as having chromothriptic characteristics; two from the APCRC are 0.43 and 0.44, which are higher than scores from their matched blood. Supplementary Fig. S4 Recurrent somatic aberrations within SAPCS, compared to AAPC (African American), TCGA, and COSMIC prostate cancer datasets. Genes or chromosome regions affected are shown next to oncoplots, with the total number of mutations within SAPCS tumors in the rightmost column. Note that a multiple hit accounts for more than one count. Abbreviations include: TFBS, transcription factor binding site; DHS, DNase I hypersensitive site; and CN, copy number. Supplementary Fig. S5 Unsupervised hierarchical clustering of SCNA segmented data observed within this study and the Memorial Sloan Kettering Cancer Center cohort (MSKCC; n = 157 primary tumors). Selected genomic regions indicative of copy number subtypes are labeled. Each column represents a genomic region. Ward's clustering with the Manhattan distance metric was applied to cluster the rows (patients) with consensus clustering. PGA, percentage of genome alteration. Supplementary Fig. S6 Model of prostate carcinogenesis among patients of African ancestry. Tajima's D statistic per chromosome of somatic SNVs present in each clone or subclone across six study participants was computed and averaged using VCFtools (Danecek et al, 2011). Abbreviations: AR, androgen receptor; PI3K, phosphoinositide 3-kinase; WNT, canonical wingless-type MMTV integration site family.