The Mitochondrial and Autosomal Mutation Landscapes of Prostate Cancer Johan Lindberg, Ian G. Mills, Daniel Klevebring, Wennuan Liu, Mårten Neiman, Jianfeng Xu, Pernilla Wikström, Peter Wiklund, Fredrik Wiklund, Lars Egevad, Henrik Grönberg  European Urology  Volume 63, Issue 4, Pages 702-708 (April 2013) DOI: 10.1016/j.eururo.2012.11.053 Copyright © 2012 European Association of Urology Terms and Conditions

Fig. 1 Significantly mutated genes in 63 prostate tumors. Center grid: Samples are ordered according to the most frequently mutated genes on a descending scale with priority given to autosomal genes. Color code: grey=no mutation; blue=protein altering single nucleotide variants/insertions and deletions; red=point mutation and deletion; green=point mutation and amplification. Upper grid: Clinical outcome. Color code: black=aggressive disease (prostate-specific antigen [PSA] level >10 ng/ml after surgery), red=biochemical recurrence (PSA range: 0.2–10 ng/ml after surgery), green=nonrecurrent disease, grey=unknown. Due to high similarity between right and left lymph node metastases found in SWE-52, only SWE-52B is presented. To avoid inflation of genes found in primary–metastasis pairs or as high-low frequency mutations in tumor samples from the same prostate, common mutations were assigned only to the tumor tissue that harbored it in highest fraction. MT-ETC=tumors with mutations in any mitochondrial electron transport chain gene. European Urology 2013 63, 702-708DOI: (10.1016/j.eururo.2012.11.053) Copyright © 2012 European Association of Urology Terms and Conditions

Fig. 2 Multilevel genomic profiling. (A) The total number of chromosomal breaks compared to the mutation rate for each tumor (number of mutations per megabase of exome sequence). Correlation excludes SWE-37 and SWE-7 with suspected mutations in mismatch repair phenotype (r=0.44, p=0.0015). (B) The total number of chromosomal breaks compared to proliferation score for each tumor. A high proliferation score implies high expression of genes related to the cell-cycle (see Supplementary Text). Tumors are colored according to the scheme in the key; tumor protein p53 (TP53)/speckle-type POZ protein (SPOP) status also is presented. The circles are scaled according to maximum postoperative prostate-specific antigen (PSA) value, as shown in the key. The colors represent the lower limit for respective clinical outcome. The tumors analyzed in this figure constitute the core of 50 primary tumors from which copy number alteration data, and RNA and exome sequencing data were available. European Urology 2013 63, 702-708DOI: (10.1016/j.eururo.2012.11.053) Copyright © 2012 European Association of Urology Terms and Conditions

Fig. 3 Estimated fraction of cells harboring single nucleotide variants (SNVs) in relation to the expression of cell cycle genes. Upper panel: The estimated number of cells harboring each SNV (points in the figure) was assessed through a Dirichlet process described by Shah and colleagues [20]. Tumors are sorted after the median number of cells harboring each variant. Color code: black=aggressive disease (prostate-specific antigen [PSA] level >10 ng/ml after surgery), red=biochemical recurrence (PSA range: 0.2–10 ng/ml after surgery), green=nonrecurrent disease, grey=unknown. Bottom panel: A loess line demonstrating the gradual increase in proliferation score as the median proportion of cells increases for each tumor. The tumors analyzed in this figure constitute the core of 50 primary tumors from which which copy number alteration data, and RNA and exome sequencing data were available. Note the two tumor samples with a suspected mutations in mismatch repair phenotype, SWE-37 and SWE-7. SWE-37 harbored a majority of low-frequency mutations, a pattern also present in other tumors, whereas SWE-7 carried a more even spectrum of frequencies despite the high mutation rate, which was not observed in any other tumor sample. European Urology 2013 63, 702-708DOI: (10.1016/j.eururo.2012.11.053) Copyright © 2012 European Association of Urology Terms and Conditions