Fig. 5

Multi-regional sampling reveals heterogeneity in CRC driver genes in adenomas independent of matched carcinoma. a–c Three samples were subjected to re-isolations from multiple, histologically defined regions. Each sample has five panels: H&E panel displays a sampling scheme with dotted lines indicating adenoma regions while solid lines represent carcinoma regions separately isolated. TP53 panel depicts the expression of TP53 protein by IHC. Scale bar 5 mm. Panel Seq. results from high-depth CRC panel sequencing where gray indicates public mutations found in all regions, and alterations in adenoma or carcinoma are shown in orange and red, respectively. Clonal Phylogeny panel shows the evolutionary relationship among clones inferred using variants from panel sequencing. The maximum likelihood tree is shown for each CRC sample. Only non-synonymous mutations are labeled; the total number of mutations per branch is indicated by black strikes (synonymous and non-synonymous). Numbers on branches correspond to bootstrap values (1000 iterations) representing nodal support. Note: some mutations are found in panel seq. and not in clonal phylogeny due to analysis discrepancies, whereby for the phylogenetic analyses, we discarded the genomic regions with copy number alterations. Nodes with bootstrap < 50% were collapsed. In the Clonal depiction panel, clonal phylogeny results are overlaid onto an outline of the H&E section to illustrate localization of clones