Figure 3. The genetic evolution of a cutaneous squamous cell carcinoma from an actinic keratosis.

A. H&E-stained section of a skin biopsy with adjacent areas of squamous cell carcinoma and actinic keratosis dissected, as indicated by the dashed lines. B. Scatter plot of mutant allele fractions in the squamous cell carcinoma and actinic keratosis reveal three clusters of mutations. C. The same scatterplot as shown in panel B with pathogenic mutations annotated. D. Copy number alterations were inferred over bins of the genome (columns) for each histologic area (rows) and are shown as a heatmap (red = gain, blue = loss, white = no change). No somatic gains or losses were observed. E. Major allele frequency – 0.5 (y-axis) for heterozygous SNPs across the genome (x-axis) show loss of heterozygosity over chromosome 9p. F. Phylogenetic tree rooted at the germline state. G and H. Immunostaining for p53 (panel G, brown stain) and phospho-MAPK (panel H, purple stain), show keratinocytes overexpressing p53 in both regions with increased phospho-MAPK in the squamous cell carcinoma.