Fig. 3

BRAF mutation is frequently followed by variant-selective amplification in SKCM. a Co-occurring (blue) and mutually exclusive (red) copy number and other mutation events with BRAF mutations. P-values were calculated using the pairwise Fisher’s exact test. b Violin plot of BRAF mRNA organized by putative copy number alteration frequency estimated by GISTIC. The horizontal line connects median values of mRNA expression in each group. c The proportion of tumors with copy gains organized by BRAF genotype and cancer type. The P-value of the binomial test was <0.05. Confidence intervals were calculated by the Clopper and Pearson exact test. d GISTIC analysis of copy-number changes in each cancer type. FDR Q values account for multiple-hypothesis testing. The significance threshold is indicated by the green line. The locations of the peak regions are indicated to the right of each panel. Chromosome positions are indicated along the y-axis with centromere positions indicated by dotted lines. The blue band delimits chromosome 7. The arrowhead indicates the position of focal amplification at 7q34 is SKCM. e Probability density function of BRAF VAF in LUAD, COAD, or SKCM. The mean is indicated in dashed line. The P-value of Welch’s t-test comparing the mean of SKCM to LUAD or COAD were <0.0001. f The dependence of VAF on the phylogenetic relationship between a locus-specific somatic copy-number gain (SCNA) and single-nucleotide variant (SNV). g Scatter plot and linear regression (dashed line) of cVAF and absolute copy-number stratified by cancer type. The slope is non-zero ( P < 0.0001). h Allelic fractions were reinterpreted as average variant copies per cancer cell (or multiplicity). Box-plots show the median, the inter-quartile range, and the minimum/maximum after excluding potential outliers. The P-value of Welch’s t-test comparing the means of SKCM to LUAD or COAD were <0.0001