Figure 3. Single-gland targeted sequencing confirms the predictions of the Big Bang model and exposes variegation in carcinomas but not adenomas.

Heat maps indicate the presence of representative public and private mutations across multiple individual glands per tumor, where targeted sequencing and whole-exome sequencing of the bulk tumor is included for comparison. In all the adenomas, private mutations are confined to a single tumor side (regional and side-specific events), whereas in invasive carcinomas the same private mutation is found in distant regions of the neoplasm, despite remaining non-dominant. These patterns of genetic variegation are indicative of sub-clone mixing in the early neoplasm followed by scattering. For representative carcinoma M, the mutational data are summarized according to the schematic in Figure 1b, where variegated mutations (red) occurred early and scattered to distant tumor regions. Regional mutations (yellow) occurred later and were confined to smaller regions of the neoplasm.