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Supplementary Figure Legends Supplementary Figure 1. Overview of the study workflow. Supplementary Figure 2. Hematoxylin & eosin stainings of samples in the study. Supplementary Figure 3. FACS ploidy histogram of Mm1702. Supplementary Figure 4. Mutation-plots demonstrating the subclonality analysis in different regions of tumor Mm1641. The subclonal fraction is obtained from the ABSOLUTE analysis. Subclonal fractions of all mutations in two regions are plotted on the x- and y-axis. Melanoma driver mutations such as BRAF mutations and mutations in the PI3K pathway are indicated in the plots. Supplementary Figure 5. Mutation-plots demonstrating the subclonality analysis in different regions of tumors Mm1641, Mm1702 and Mm1749. The subclonal fraction is obtained from the ABSOLUTE analysis. Subclonal fractions of all mutations in two regions are plotted on the x- and y-axis. Melanoma driver mutations such as BRAF mutations and mutations in the PI3K pathway are indicated in the plots. Supplementary Figure 6. Mutation-plots demonstrating the subclonality analysis in different regions of tumor Mm1749. The subclonal fraction is obtained from the ABSOLUTE analysis. Subclonal fractions of all mutations in two regions are plotted on the x- and y-axis. Melanoma driver mutations such as BRAF mutations and mutations in the PI3K pathway are indicated in the plots. Supplementary Figure 7. Mutation-plots demonstrating the subclonality analysis in different regions of tumors Mm1749, Mm1765 and Mm1767. The subclonal fraction is obtained from the ABSOLUTE analysis. Subclonal fractions of all mutations in two regions are plotted on the x- and y-axis. Melanoma driver mutations such as BRAF mutations and mutations in the PI3K pathway are indicated in the plots. Supplementary Figure 8. Mutation-plots demonstrating the subclonality analysis in different regions of tumors Mm1767, Mm1772 and Mm1837. The subclonal fraction is obtained from the ABSOLUTE analysis. Subclonal fractions of all mutations in two regions are plotted on the x- and y-axis. Melanoma driver mutations such as BRAF mutations and mutations in the PI3K pathway are indicated in the plots. Supplementary Figure 9. Correlations of trunk and non-trunk mutations to signatures from Alexandrov et al Nature 2013. Supplementary Figure 10. Difference in expression levels between tumor regions harboring non-trunk mutations (“mutated regions”) and those missing the corresponding mutations (“wildtype regions”). Average expression of wildtype regions was subtracted from the average expression of mutated regions. Genes with at least 1 mutant read were plotted, to disregard genes that were exclusively expressed in surrounding non-malignant cells. The light-blue bar indicates the median value, and the dashed black line indicates zero expression difference. P-value from Wilcoxon test. Pvalue for the combined values diverging from zero is 0.06. Supplementary Figure 11. Correlation plots between DNA and RNA VAF in individual regions in tumors Mm1641 and Mm1702. Red color indicates significant values using a binomial test as described in Supplemental information. Cor. denotes Spearman correlation value between DNA and RNA VAF. Supplementary Figure 12. Correlation plots between DNA and RNA VAF in individual regions in tumors Mm1702, Mm1742 and Mm1749. Red color indicates significant values using a binomial test as described in Supplemental information. Cor. denotes Spearman correlation value between DNA and RNA VAF. Supplementary Figure 13. Correlation plots between DNA and RNA VAF in individual regions in tumors Mm1749 and Mm1765. Red color indicates significant values using a binomial test as described in Supplemental information. Cor. denotes Spearman correlation value between DNA and RNA VAF. Supplementary Figure 14. Correlation plots between DNA and RNA VAF in individual regions in tumors Mm1767 and Mm1772. Red color indicates significant values using a binomial test as described in Supplemental information. Cor. denotes Spearman correlation value between DNA and RNA VAF. Supplementary Figure 15. Correlation plots between DNA and RNA VAF in individual regions in tumor Mm1837. Red color indicates significant values using a binomial test as described in Supplemental information. Cor. denotes Spearman correlation value between DNA and RNA VAF.